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1

Robert, Catherine. "Approche du diagnostic des infections à herpesvirus humain-6 (HHV-6) par des techniques immunoenzymatiques." Paris 11, 1996. http://www.theses.fr/1996PA114837.

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2

Herbein, Georges. "L'infection à Herpesvirus humain type 6 (HHV-6) chez les transplantés : une étude rétrospective de 32 patients." Université Louis Pasteur (Strasbourg) (1971-2008), 1991. http://www.theses.fr/1991STR1M098.

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3

Manichanh, Chaysavanh. "Etude phénotypique et génotypique de la résistance du sixième herpesvirus humain (HHV-6) aux antiviraux." Paris 6, 2001. http://www.theses.fr/2001PA066458.

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4

André-Garnier, Élisabeth Imbert-Marcille Berthe Marie. "Cytomegalovirus et Herpesvirus Humain de type 6 étude de leur réplication au sein du système hématopoïétique /." [S.l.] : [s.n.], 2003. http://theses.univ-nantes.fr/thesemed/DOCandre.pdf.

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5

André-Garnier, Élisabeth. "Cytomegalovirus et Herpesvirus Humain de type 6 : étude de leur réplication au sein du système hématopoi͏̈étique." Nantes, 2003. http://archive.bu.univ-nantes.fr/pollux/show.action?id=f5645905-5676-4dcd-adbc-d9cc1c12ffc6.

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Le Cytomégalovirus humain (CMVH) et l'Herpèsvirus humain de type 6 (HHV6) sont deux ?- Herpesvirinae présentant un tropisme majeur pour le système hématopoi͏̈étique. Ce travail a visé à évaluer leurs capacités de réplication au cours de la différenciation hématopoi͏̈étique. Des outils méthodologiques autorisant la mise en évidence de la réplication virale ont été développés, permettant la détection de transcrits viraux tardifs par RT-PCR. Parmi les marqueurs développés pour le CMVH, l'ARNm tardif UL22, issu d'un épissage, a montré son intérêt, en particulier dans le cadre du diagnostic de l'infection active/maladie à CMVH. Pour l'HHV6, la détection du transcrit tardif multi-épissé de la gp 82-105 (U100) et la mise en évidence en cytométrie de flux d'antigènes nucléaires tardifs ont été développés à partir de cultures de souches virales de variant B. Ces essais ont permis de préciser que la forme épissée du gène U100 est exprimée en phase tardive du cycle de réplication, alors que la forme non épissée est un marqueur de la phase précoce. La possibilité de survenue d'une réplication des deux virus au cours de l'expansion ex vivo de 10 prélèvements de cellules souches hématopoi͏̈étiques CD34+ périphériques, a ensuite été envisagée. Ces essais ont été réalisés dans le cadre d'une nouvelle approche thérapeutique, qui vise à réduire la durée d'aplasie, chez des sujets traités par hautes doses de chimiothérapie, grâce à l'injection de cellules souches différenciées in vitro. Les cultures ont été menées en milieu liquide, en présence de cytokines permettant d'engager la différenciation vers les lignées myéloi͏̈des et monocytaires. Parmi les quatre cultures de cellules provenant de patients séropositifs pour le CMVH, aucun marqueur de réactivation virale n'a été détecté. A l'inverse, dans 5/10 cultures issues de prélèvements effectués chez les patients séropositifs pour l'HHV6, le transcrit U100 a été amplifié. Ces données montrent pour la première fois et sans avoir recours à une infection préalable par une souche virale, une réplication de l'HHV6 due à une réactivation au cours de la différenciation des progéniteurs hématopoi͏̈étiques. Ces résultats originaux soulèvent le problème de la sécurité virale lors des réinjections chez des patients immunodéprimés de cellules supportant une réplication de l'HHV6
Cytomegalovirus (CMV) and Human Herpesvirus 6 (HHV6) were two ? -Herpesvirus with a major tropism for hematopoietic system. Since their interactions with hematopoiesis are still poorly understood, we evaluated their replication capacity during differenciation of hematopoietic stem cells. We first developed and evaluated tools to follow viral replication, by detection of late viral transcripts, which assess occurrence of a complete replication cycle. Among the CMV transcripts amplified by reverse transcription-PCR, the late spliced UL22 mRNA was of particular interest, notably to predict the occurrence CMV disease during active infection. For HHV6, a one-step RT-PCR amplifying the late alternatively U100 gene encoding the gp 82-105 glycoprotein and a flow cytometry method to analyse nuclear late antigens were developed from reference strains cultures. Evaluation of these methods was then realized during a sequential culture of HST strain on MT4 cells. This allows to specify that the U100 gene splicing starts at a late stage of multiplication whereas unspliced forms were detectable earlier in the cycle. We then evaluated the occurrence of viral replication during ex vivo expansion of 10 peripheral hematopoietic stem cells (CD34+) samples. Cultures were maintained in a serum free liquid medium supplemented with cytokines of myeloid-monocyte lineage. Neither CMV DNA nor CMV UL22 or UL86 mRNA were detected among the 4 cultures from CMV seropositive patients. Conversely, the late alternatively spliced U100 mRNA (HHV6) was detected at day 14 or 21 in 5/10 cultures from HHV6 seropositive patients. Our data demonstrated for the first time that HHV6 could enter in a replicative cycle during hematopoietic differenciation in the absence of in vitro infection of cells. This also raised the question of the viral safety of the infusion of ex-vivo expanded CD34-positive PBPCs
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6

Gautheret-Dejean, Agnès. "Etude des interactions entre les sixieme et septieme herpesvirus humains (hhv-6, hhv-7) et le virus de l'immunodeficience humaine (hiv) chez l'homme." Paris 11, 1997. http://www.theses.fr/1997PA114842.

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7

Jaworska, Joanna. "Role for the immediate-early 1 protein of human herpesvirus 6 in innate immune evasion." Thesis, Université Laval, 2010. http://www.theses.ulaval.ca/2010/26876/26876.pdf.

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8

Poirel, Laurent. "Caracterisation genetique, epidemiologie et pouvoir pathogene des nouveaux herpesvirus lymphotropes (hhv-6, hhv-7, hhv-8) (doctorat : microbiologie)." Paris 11, 1999. http://www.theses.fr/1999PA114822.

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9

Sifer, Christophe. "Mise au point d'un système de RT-PCR pour la mise en évidence d'un ARN messager tardif du sixième herpesvirus humain." Paris 5, 1998. http://www.theses.fr/1998PA05P189.

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10

Reynaud, Joséphine. "Développement d'un modèle murin transgénique d'infection par l'herpèsvirus 6A et étude des mécanismes d'induction de la neuroinflammation." Phd thesis, Ecole normale supérieure de lyon - ENS LYON, 2013. http://tel.archives-ouvertes.fr/tel-00998378.

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L'herpèsvirus humain (HHV) 6 est un betaherpèsvirus largement répandu, associé à plusieurs maladies neuroinflammatoires, telles que des encéphalites ou la sclérose en plaques (SEP). Cependant, les mécanismes impliqués dans la neuropathologie induite par les deux espèces d'HHV-6, HHV-6A et HHV-B, sont peu connus. De plus, l'absence de modèle d'infection chez le petit animal a ralenti l'étude de la pathogénèse virale. Dans ce contexte, nous avons développé un modèle d'infection par HHV-6 chez des souris transgéniques, qui expriment la protéine CD46 humaine, identifiée comme récepteur cellulaire pour HHV-6. Nous avons pu démontrer une persistance de l'ADN viral d'HHV-6A, mais pas d'HHV-6B, dans le cerveau de souris transgéniques pendant plusieurs mois. De plus nos résultats montrent qu'HHV-6A induit la sécrétion de chimiokines pro-inflammatoires par les cellules neurales murines et provoque l'infiltration de cellules immunitaires dans le cerveau de souris infectées. Enfin, HHV-6A, mais pas HHV-6B, pourrait induire des réponses cellulaires chez les cellules murines via le récepteur de l'immunité innée TLR9 (toll-like receptor 9). En collaboration avec une équipe de Grenoble, nous avons ensuite montré que l'infection par HHV-6A induit l'expression de rétrovirus endogènes humains (HERV) dans des cellules mononuclées et des lignées neurales humaines. Ces HERV, en particulier leurs protéines d'enveloppe qui présentent des propriétés pro-inflammatoires, sont associés à diverses maladies autoimmunes dont la SEP. HHV-6A pourrait donc participer au développement de pathologies inflammatoires via l'induction de ces HERV. L'ensemble de ces travaux supporte ainsi l'existence d'un lien entre l'infection par HHV-6A et la neuroinflammation, et apporte de nouvelles pistes quant aux mécanismes potentiellement impliqués.
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11

Ng, Hoi-yee Iris, and 吳凱怡. "Human herpesvirus 6 (HHV-6) mRNA in peripheral blood leukocytes differentiates active infection from latency." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31226589.

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12

Ng, Hoi-yee Iris. "Human herpesvirus 6 (HHV-6) mRNA in peripheral blood leukocytes differentiates active infection from latency /." Hong Kong : University of Hong Kong, 2002. http://sunzi.lib.hku.hk/hkuto/record.jsp?B24520895.

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13

Yoshikawa, Tetsushi. "Human herpesvirus 6 iInfection in transplantation." Nagoya University School of Medicine, 2001. http://hdl.handle.net/2237/5363.

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14

Kidd, Ian Michael. "Human cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 infection of the immunocompromised host." Thesis, University College London (University of London), 1997. http://discovery.ucl.ac.uk/1453654/.

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15

Lyall, Elizabeth Grace Hermione. "Human herpesvirus virus 6 (HHV-6) infection in immunocompromised children." Thesis, University of Edinburgh, 1999. http://hdl.handle.net/1842/22427.

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The current study was designed, to include a retrospective serological assessment of HHV-6 antibody responses in samples taken from children at presentation with malignancy and sequentially during treatment. An indirect fluorescent antibody test (IFA) and an enzyme linked immunosorbent assay (ELISA) were used to detect HHV-6 lgG, and selected samples were tested for HHV-6 lgM by IFA. The paediatric patients, whether solid tumour or leukaemic patients, had a similar response to HHV-6 as age matched controls and almost all (97%) had lgG to the virus at the time of presentation. Acquisition of a response to more than one herpesvirus increased with age in the patients and where there was only a response to one virus it was usually HHV-6. Antibody responses to CMV and VZV were similar in patients and controls. Sequential samples from patients during immunosuppressive treatment showed a gradual decline over time in ELISA index for lgG to HHV-6 and no reactivations of HHV-6 were seen. lgM to HHV-6 was produced by one child with a primary CMV seroconversion but HHV-6 reactivation could not be confirmed as the possibility of cross reactive antibody was not excluded by a cross absorption experiment. A prospective analysis of HHV-6 DNA in saliva and serum was undertaken on new patients presenting between August 1992 - August 1993. HHV-6 is secreted in the saliva of those previously infected, and presence of HHV-6 in the serum implies an active viraemia. Saliva was collected prospectively from new patients, from siblings and from volunteer healthy controls. Serum was collected from patients during treatment. A nested PCR for HHV-6 was developed. The sequence of DNA chosen for amplification contained a cleavage site for the restriction endonuclease Hind 111 which enabled type "A" and "B" HHV-6 to be identified in any PCR positive samples. HHV-6 DNA (type "B") was commonly found in the saliva of healthy controls (74%) and patients (58%), but patients who were febrile, unwell and neutropaenic less frequently secreted HHV-6 in the saliva supernatant (18%). Whether this was a local effect of chemotherapy on the salivary glands was considered. HHV-6 DNA was not detected in any serum samples, suggesting no evidence of active viraemia. The potential role of HHV-6 as a serious pathogen in immunosuppressed patients remains to be fully elucidated, but in this limited study of a small paediatric cohort of oncology patients no evidence of deleterious virus activity was found.
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16

Thomasini, Ronaldo Luís 1978. "Citomegalovírus, herpesvírus humano 6, herpesvírus humano 7 e perfil imunofenotípico do infiltrado inflamatório na periodontite crônica marginal." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311940.

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Orientador: Sandra Cecília Botelho Costa
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Periodontite humana crônica é um processo inflamatório caracterizado por denso acúmulo de células imunes no tecido periodontal. A periodontite pode levar a perda do dente no paciente e a patogênese desta doença não é completamente conhecida. Este estudo testou a hipótese de que as células do infiltrado inflamatório podem abrigar betaherpesviruses e estes vírus estão ligados á subpopulação específicas de linfócitos. Fragmentos de tecido periodontal foram obtidas de pacientes afetados por periodontite e de indivíduos saudáveis. Imuno-histoquímica foi realizada para a contagem de células CD19+, céulas CD3+ e células CD4+ e CD8+. Reação em cadeia da polimerase e imuno-histoquímica foram realizados para detectar citomegalovírus, herpesvirus humanos 6 e 7 nas amostras. Como esperado, os tecidos coletados de indivíduos saudáveis não apresentaram nível significativo de infiltrado inflamatório e, portanto, foram excluídos dos procedimentos de imunofenotipagem. Os resultados mostraram que células CD19+ foram discretamente predomiantes sobre as células CD3+ no tecido periodontal afetado, mas estatisticamente não significativo. A subpopulação CD4+ de linfócitos estava significativamente em maior número que a subpopulação CD8+ de linfócitos (P=0,004), nas amostras. Citomegalovírus e herpesvírus humano 7 foram encontrados em locais afetados, mas não no tecido coletado de indivíduos saudáveis (P=0,04 e P=0,04, respectivamente). Herpesvirus humano 6 foi raramente detectado. Foi encontrado correlação entre citomegalovírus com menor relação de CD19+/CD3+ (P=0,003) e herpesvirus humano 7 com menor relação CD19+/CD3+ (P=0,003) e maior relação de CD4+/CD8+ ( P=0,002). Imuno-histoquímica foi negativa para citomegalovírus, herpesvirus humano 6 e herpesvirus humano 7 em todas as amostras. Este estudo mostra que citomegalovírus e herpesvírus humano 7 podem estar presentes em regiões afetadas pela periodontite, mas são incomuns em regiões saudáveis. Além disso, este estudo sugere que citomegalovírus pode ser relacionado ao infiltrado inflamatório, com predomínio de células CD3+ e, herpesvirus humano 7 pode estar relacionado ao infiltrado inflamatório com predomínio de células CD4+. Os dados sugerem que citomegalovírus e herpesvírus humano 7 podem estar presentes no infiltrado inflamatório, em estado de latência. No entanto, outros métodos deveriam ser realizados para confirmar esta hipótese
Abstract: Human chronic periodontitis is an inflammatory process characterized by dense accumulation of immune cells in the periodontal tissue. The periodontitis can lead to loss of teeth in the patient and the pathogenesis of this disease is not completely known. This study tested the hypothesis that cells within inflammatory infiltrate can harbor betaherpesviruses and these viruses are linked to specific lymphocyte subpopulation. Biopsies of periodontal tissue were taken from periodontitis affected and from healthy subjects. Immunohistochemistry was performed to count CD19+ cells, CD3+ cells, CD4+ and CD8+ cell subsets. Polymerase chain reaction and immunohistochemistry were performed to detected cytomegalovirus, human herpesvirus 6 and 7 in the samples. As expected, tissues collected from healthy subjects presented no significant level of inflammatory infiltration and therefore were excluded from immunostaining procedures. The results showed that CD19+ cells had discrete predominance over CD3+ cells in the periodontitis affected tissue but not statistically significant. CD4+ lymphocyte subset were significantly higher then CD8+ lymphocyte subset (P=0.004) in the samples. Cytomegalovirus and human herpesvirus 7 were found in affected sites but not in tissue collected from healthy subjects (P=0.04 and P=0.04, respectively). Human herpesvirus 6 was rarely detected. We found a correlation between cytomegalovirus with lower CD19+/CD3+ ratios (P=0.003) and human herpesvirus 7 with lower CD19+/CD3+ ratio (P=0.003) and higher CD4+/CD8+ ratios (P=0.002). Imunohistochemistry was negative for cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 in the total of samples. This study shows that cytomegalovirus and human herpesvirus 7 can be present in periodontitis affected sites but are uncommon in healthy sites. Moreover, this study suggests that cytomegalovirus can be related to inflammatory infiltrate with predominance of CD3+ cells and, human herpesvirus 7 can be related to inflammatory infiltrate with predominance of CD4+. The data suggest that cytomegalovirus and human herpesvirus 7 could be present in the inflammatory infiltrate in latent state. However, different methods should be performed to confirm this hypothesis
Doutorado
Ciencias Basicas
Doutor em Clínica Médica
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17

Nowak, Monika. "Human herpesvirus-6-induced cytokines and lymphocyte anergy." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0009/NQ28364.pdf.

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18

Lawrence, Glenda L. "Sequence analysis of the human herpesvirus-6 genome." Thesis, University of Cambridge, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.386182.

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19

Faro, Eduardo Salustino. "Epidemiologia molecular do herpesvírus humano tipo 6 (HHV-6) em crianças recém-nascidas e suas respectivas mães." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-06012009-162645/.

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A infecção primária com o herpesvirus humano tipo 6 (HHV-6) pode resultar no exantema súbito, encefalite e recorrentes complicações. Pesquisas demonstram que crianças obtêm os anticorpos contra o HHV-6 antes dos dois anos de idade. Após a infecção primária, o DNA do HHV-6 permanece latente em linfócitos, saliva ou líquor. A rota de transmissão permanece controversa. A liberação do HHV-6 em saliva parece ser a maior rota de transmissão. A transmissão intra-uterina, integrada no cromossomo é outra sugestão de transmissão. Foram colhidas 172 amostras, 86 de secreção cervical (mãe) e 86 de aspirado de nasofaringe (filho). Utilizamos a técnica de nested PCR para detecção do DNA viral do HHV-6. Das amostras positivas, 64% foram detectadas na secreção cervical. A positividade mãe-recém nascido foi de 14%. Das amostras de nasofaringe positivas, 25% não tiveram pareamento de positividade com as secreções cervicais de suas mães. Com estes resultados sugerimos que está existindo uma passagem viral do HHV-6, da mãe para o seu recém-nascido antes do nascimento.
The primary infection with the human herpesvirus type 6 (HHV-6) can result in sudden exanthema, encephalitis and recurrent complications. Research data show that children obtain antibodies against the HHV-6 before two years old. After the primary infection, the HHV-6 DNA remains latent in lymphocytes, saliva, or spinal fluid. The transmission route remains controverse. The HHV-6 elimination of saliva seems to be the major transmission route. Intrauterine transmission, integrated in the chromosomes, is another suggested route of transmission. A total of 172 samples was collected, including 86 cervical secretion samples (mother) and 86 nasopharyngeal aspirates (newborn). We used the nested PCR technique for HHV-6 DNA detection. Among the positive samples, 64% were detected in cervical secretion. The co-positivity between mother and newborn was 14%. Among the positive nasopharyngeal samples, 25% did not present co-positivity with the cervical secretion samples of the respective mothers. Based on our results, we suggest the existence of HHV-6 transference from the mother to the fetus before birth.
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20

Parola, Daniela Corte. "Herpesvirus humano 5,6 e 7 (HHV-5, HHV-6 e HHV-7) em receptores de transplantes de medula ossea." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311928.

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Orientador: Sandra Cecilia Botelho Costa
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: O membro protótipo da subfamília dos betaherpesvírus, o citomegalovírus humano (HCMV), é o patógeno mais importante em pacientes transplantados, incluindo aqueles que receberam células de medula óssea ou enxerto de células tronco. Testes diagnósticos para identificar precocemente a infecção ativa pelo HCMV e uma terapia antiviral pré-clínica são medidas significantes para o controle desse vírus. Dois betaherpesvírus descobertos recentemente, o herpesvírus humano 6 (HHV-6) e o herpesvírus humano 7 (HHV-7) são geneticamente mais próximos um ao outro do que ao HCMV. Ambos têm alta prevalência na população em geral. Esses vírus não são tão patogênicos quanto o HCMV, porém o HHV-6 pode causar doenças como encefalite, hepatite e supressão da medula óssea. O objetivo do presente estudo foi avaliar o impacto clínico desses três vírus em transplantados de medula óssea. A monitorização pela N-PCR é importante método precoce para o controle da infecção ativa ou da doença pelo HCMV. A reação em cadeia da polimerase tipo nested (N-PCR) foi utilizada prospectivamente na monitorização de 43 pacientes para identificar as infecções ativas e a doença causada pelo HCMV, HHV-6 e HHV-7 por um período superior a 150 dias pós-transplante. Quarenta e um pacientes receptores adultos de células de medula óssea ou células tronco, com doença maligna e dois pacientes com doença não-maligna foram incluídos nesse estudo. Aciclovir foi administrado em baixas doses, como terapia profilática para infecção por herpesvírus tipo 1. Pacientes com infecção ativa por HCMV receberam terapia pré-clínica com ganciclovir. As incidências de positividade para infecção ativa por HCMV no sangue periférico, HHV-6 e HHV-7 no soro detectadas por N-PCR foram de 72%, 4,6% e 13,9%, respectivamente. A doença por HCMV ocorreu em 8 dos 43 pacientes (18,9%), no trato gastrintestinal e todos apresentaram N-PCR positiva para infecção por HCMV e um apresentou N-PCR positiva para HHV-6 no soro. Nenhum dos pacientes com doença por HCMV apresentou infecção ativa por HHV-7. A infecção ativa foi por HHV-6 e HHV-7 foi baixa em nossa casuística. A doença por HCMV permanece a mais a causa mais importante de impacto clínico após o transplante de medula óssea. Estudos adicionais necessitam serem feitos para uma melhor compreensão da relação entre os herpesvírus HCMV, HHV-6 e HHV-7 nos pacientes transplantados de medula óssea e células tronco periféricas
Abstract: The prototype member of the Betaherpesvirus subfamily, human cytomegalovirus (HCMV), is the most important infectious pathogen in transplant recipients, including those receiving bone marrow (BM) or stem cell (SC) grafts. Rapid diagnostic tests to identify active CMV infection, and pre-emptive therapy are significant improvements in the management of CMV. Two newly identified betaherpesviruses, human herpesvirus-6 (HHV-6) and human betaherpesvirus-7 (HHV-7), are genetically more closely related to each other than to CMV. Both are highly prevalent in the general population. These viruses are not as pathogenic as CMV but HHV-6 can cause disease such as encephalitis, hepatitis and bone marrow suppression. The aim of this study was to evaluate the clinical impact of these three viruses in bone marrow and stem cell transplantation patients. Monitorization with Nested-PCR is important in the control of active CMV infection or disease. Nested polymerase chain reaction (N-PCR) was used prospectively to monitor 43 patients for evidence of active infections and diseases caused by HCMV, HHV-6 and HHV-7 for up to 150 days after transplant. Forty-one adult recipients of BM or SC graft with malignant diseases and two patients with non-malignant diseases, and with a risk for CMV disease (D+/R+; D+/R-) were enrolled in this study. Aciclovir was used before the transplant at low doses, as prophylactic therapy for HHV-1. Patients with active CMV infections received pre-emptive therapy with ganciclovir. The incidence of positive active HCMV in blood, HHV-6 and HHV-7 in serum detected by Nested-PCR was 72%, 4.6% and 13.9%, respectively. HCMV disease occurred in 8/43 patients (18.6%), in the gastrointestinal tract and all presented positive N-PCR for active HCMV infection and one presented active infection by HHV-6 detected in serum. None of the patients presented active HHV-7 infection. Co-infection by HHV-6 and HHV-7 was low. CMV disease remains the most important disease after BMT. Future studies can be made to a better understanding in relationship between HCMV, HHV-6 and HHV-7 in BM or SC transplantation recipients
Mestrado
Ciencias Basicas
Mestre em Clinica Medica
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21

Fok, Yuen-kei Vivien. "Expression of human herpesvirus 6 (HHV-6) genes in virus-infected cells /." View the Table of Contents & Abstract, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31385515.

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22

Fok, Yuen-kei Vivien, and 霍沅琪. "Expression of human herpesvirus 6 (HHV-6) genes in virus-infected cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B45010006.

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23

Wang, Fu-Zhang. "Human herpesvirus 6 infection after allogeneic stem cell transplantation /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3589-0/.

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24

Bell, Adam Joseph. "Inherited chromosomally integrated human herpesvirus 6 : demographics and disease." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7073/.

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Human herpesvirus (HHV) –6A and HHV-6B are unique among herpesviruses in their ability to integrate into the telomeres of human chromosomes and be inherited in a Mendelian fashion. Based on current data, inherited chromosomally integrated HHV-6 (iciHHV-6) is present in 0.5-2% of the UK population. There is increasing evidence to suggest that iciHHV-6 is not a dead-end for the virus, and that HHV-6 can be excised from the genomes of iciHHV-6-positive individuals. It is hypothesised that this excision occurs from the formation of T-loops between the end of the telomere and the viral telomere like repeats (TLRs). T-loops form naturally in a cell as part of the complex that protects the end of the chromosomes; however, under certain circumstances these can be excised leading to a loss of telomeric repeats from the chromosome and the formation of circular, extra-chromosomal telomeric sequence. There is increasing evidence that excision can lead to reactivation of the virus and potentially cause disease. Our current understanding of the phenotypic associations of iciHHV-6 is based on case-reports and case-control studies of individual diseases. The work presented in this thesis set out to answer a number of questions regarding the phenotypic consequences, and genome dynamics of iciHHV-6. First, the association between both exogenously acquired HHV-6 and iciHHV-6 and classical Hodgkin lymphoma (cHL) was examined in a case-control study. Whilst exogenously acquired HHV-6 was significantly associated with cHL the virus was present at low levels in DNA extracted from cHL tumours. Virus at such low level was concluded as not having a direct role in the pathogenesis of cHL. A case control study of iciHHV-6 and cHL revealed no difference in the prevalence of iciHHV-6 amongst cases and controls, but identified a single iciHHV-6-positive individual who appeared to have four integrated viral genomes. Secondly, iciHHV-6 was examined in the Generation Scotland: Scottish Family Health Study (GS:SFHS) cohort, in a hypothesis generating study. It was revealed the iciHHV-6 was present at a prevalence of 2.7%. Further analysis showed a statistically significant difference in the prevalence of iciHHV-6 between individuals born in Scotland (2.8%) and England (1.8%). Analysis of disease phenotypes revealed potential associations between iciHHV-6 and breast cancer in an unrelated subset of the GS:SFHS cohort. Also confirmed was the recent 3 report of an association between iciHHV-6 and angina pectoris. Analysis of other variables revealed iciHHV-6-positive females had a lower average Mill Hill vocabulary test score than iciHHV-6-negative females; and that iciHHV-6-positivity was associated with participation in fewer years of education. Thirdly, the iciHHV-6 genome in an LCL generated from an iciHHV-6A-positive individual was shown to be dynamic. The gross structure of the HHV-6 genome is a unique (U) region flanked by direct repeats (DR) (DR.U.DR).Analysis using droplet digital PCR (ddPCR), on DNA extracted at various time points of the LCL culture revealed that viral sub-genomic regions were lost in a proportion of cells, which coincided with a reduction in population doublings of the culture. At the point of reduction of viral copy number, an excess of HHV-6 DRs was noted suggesting that only a portion of the viral genome had been lost in these cells. Gradually the viral copy number returned to approximately one copy per cell. It is likely this was caused by an outgrowth of cells where excision had not occurred. This in vitro model demonstrated that whilst excision of iciHHV-6 genomes is possible, it may be accompanied by a reduction in cell viability. Loss of HHV-6 genomic regions was also examined in 59 iciHHV-6-positive individuals and was infrequent. Only six showed some degree of DR loss. Further to this, inheritance of single direct repeats was observed in six individuals and two families in the GS:SFHS cohort. A novel ddPCR and mathematical model was developed to predict the iciHHV-6 genome configuration in samples where atypical U:DR ratios were observed. Through this, we hypothesise that an iciHHV-6-positive individual who had 4 U regions per cell and 5 DR regions per cell, had an integrated HHV-6A genome concatemer with the configuration (DR.U)4.DR, and hypothesised that this arose from integration of a replication intermediate. Finally, phylogenetic analysis of five regions of 26 iciHHV-6 genomes and their counterparts in exogenously acquired HHV-6 genomes was performed. There was a higher degree of divergence between iciHHV-6A and exogenous HHV-6, along with evidence of a common viral ancestor in four iciHHV-6-positive individuals. This divergence was not observed in iciHHV-6B were very little variation was observed between iciHHV-6B and exogenously acquired HHV-6B. These results shed light on the complex relationship between iciHHV-6 and the human host.
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25

Thomasini, Ronaldo Luís 1978. "Detecção e monitorização do Herpesvirus humano 7 (HHV-7) em transplantados hepaticos : impacto clinico e associação com Citomegalovirus e Herpesvirus humano 6." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311931.

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Orientador: Sandra Cecilia Botelho Costa
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Neste estudo, 29 pacientes adultos, transplantados de fígado foram monitorados (até 180 dias pós-transplante) para infecções ativas por HCMV, HHV-6 e HHV-7 usando Nested-PCR (N-PCR). O protocolo de imunossupressão foi baseado na combinação de esteróides e ciclosporina e profilaxia com ganciclovir não foi usada. Aciclovir foi usado como profilaxia para o Herpes simples. Um grupo controle foi estudado, N-PCR em DNA extraído de PBL e soro de 53 indivíduos sadios foram realizados. Destes indivíduos, 8 amostras de saliva foram coletadas para isolamento do HHV-7 e produção de controle positivo. DNA do HHV-7 foi detectado em 87,5% de saliva, em 28,3% de PBL e 0% de soro. Isolamento do vírus mostrou ser 100% correlato com N-PCR. Soro foi considerado a amostra de escolha para detectar infecção ativa por HHV-7. DNA do HHV-6, HHV-7 e HCMV foram, frequentemente, detectados em pacientes após transplante hepático (65,5%, 51,7% e 48,2%, respectivamente). A maioria dos pacientes com infecção ativa por mais que um vírus é infectado de forma seqüencial e não concorrente. Infecção ativa por HHV-7 ocorreu em muitos casos antes da infecção ativa por HCMV e/ou HHV-6 indicando que ele poderia ser um fator para reativação daqueles vírus. Nested-PCR para HCMV teve valor preditivo positivo de 50% e valor preditivo negativo de 100% para infecção sintomática. Neste estudo, o HCMV foi relacionado disfunção do enxerto, HHV-6 foi associado com pneumonite, encefalite, disfunção e rejeição do enxerto e predisposição para infecção oportunista. Em pacientes livres de HCMV e/ou HHV-6, nenhuma manifestação clínica nem achados laboratoriais significativos foram relacionados ao HHV-7. O tratamento antiviral com ganciclovir foi considerado satisfatório para o HCMV, mas para o HHV-6 e HHV-7, os dados não foram conclusivos. O aciclovir poderia ter demonstrado uma limitada atividade contra o HHV-7
Abstract: In this study, 29 adult liver transplant patients were monitored (until day 180th posttransplantation) for HCMV, HHV-6 e HHV-7 active infections using Nested-PCR (N-PCR). Immunosuppression protocol was based on combinations of steroids and cyclosporine and no ganciclovir prophylaxis was used. Aciclovir was employed as Herpes simplex prophylaxis. A control group was studied; N-PCR in DNA extracted from PBL and serum of 53 healthy individuals was carried out. From these individuals, 8 samples of saliva were collected to design a positive control to N-PCR. HHV-7 DNA was detected in 87.5% of saliva, in 28.3% of PBL and 0% of serum. Virus isolation showed to be 100% correlated with N-PCR. Serum was considered to be the sample of choice to detect HHV-7 active infection. HHV-6, HHV-7 and HCMV DNA were frequently detected in patients after liver transplant (65.5%, 51.7% and 48.2%, respectively). The results show that few patients remain negative to active infection with betaherpesviruses after liver transplantation. Most of the patients with active infection with more than one virus were infected sequentially and not concurrently. HHV-7 active infection occurred in most of cases prior HCMV and HHV-6 active infections indicating that it could be a factor to reactivation of these viruses. HCMV Nested-PCR presented positive predictive value of 50% and negative predictive value of 100%. In this study, HCMV was related with graft dysfunction, HHV-6 was associated with pneumonitis, encephalitis, liver dysfunction, graft rejection and predisposition to opportunist infections. In HCMV and/or HHV-6 free patients, no clinical manifestation nor significant laboratory findings was related to HHV-7. Ganciclovir Antiviral treatment was considered satisfactory to HCMV symptomatic infections but to HHV-6 and HHV-7, no conclusive data was found. Aciclovir could be a limited activity against HHV-7
Mestrado
Farmacologia
Mestre em Farmacologia
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26

Ahlqvist, Jenny. "Differences in tropism and viral assembly pathways of human herpesvirus 6A and 6B (HHV-6A and 6B) and association of host cell proteins in HHV-6A virions /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-214-9/.

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27

Silva, Ana Carolina Guardia da 1980. "Avaliação da cinética viral do Herpesvirus Humano 6 e Citomegalovirus por PCR em tempo real e das complicações clínicas relacionadas ocorridas após o transplante de fígado." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309659.

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Orientadores: Ilka de Fatima Santana Ferreira Boin, Raquel Silveira Bello Stucchi
Tese (doutorador) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: As infecções oportunistas constituem um dos principais problemas para os transplantados de fígado. O Citomegalovírus (CMV) e o Herpesvirus humano 6 (HHV- 6) são patógenos oportunistas freqüentes nesses pacientes, e o HHV-6 tem sido associado a várias desordens tais como a encefalite. A PCR em tempo real (RT-PCR) é o padrão ouro de diagnóstico para os herpesvirus, pois tem melhor precisão, maior rendimento e menos risco de contaminação em comparação com outros testes convencionais. Objetivo: Este estudo teve como objetivo avaliar a cinética viral do HHV-6 e CMV por RT-PCR nos pacientes submetidos ao transplante hepático correlacionando-a com a presença de encefalite e complicações clínicas ocorridas no período pós-transplante. Método: Foram analisadas prospectivamente pela RT- PCR a carga viral do CMV e HHV-6 de 30 pacientes transplantados de fígado. A monitorização dos pacientes foi realizada prospectivamente desde o pré-transplante (imediatamente antes do ato cirúrgico - dia zero) com amostras do doador e receptor, e no pós-transplante: 2ª, 3ª, 4ª, 6ª, 8ª, 10ª e 12ª semanas, somando 270 amostras de soro. O protocolo foi seguido de acordo com os requerimentos para pesquisas e foi aprovado pelo Comitê de Ética em Pesquisada da Faculdade de Ciências Médicas da Universidade Estadual de Campinas (CEP nº 430/2003). Os achados clínicos foram obtidos através dos prontuários. Para a detecção e quantificação do DNA dos vírus CMV e HHV-6 foram usados os Kits comerciais "CMV Real-TM Quant" e "HHV-6 Real-TM Quant". Os testes de Nested-PCR e antigenemia foram realizados rotineiramente para o vírus CMV, pelos laboratórios do HC-Unicamp, e seu resultados obtidos eletronicamente. A análise estatística comparou as variáveis categóricas usando o teste exato de Fisher. Para identificar os fatores associados ao aumento da carga viral foi utilizado o método das Equações de Estimação Generalizadas e medidas de acurácia. Resultados: Treze (43%) dos 30 pacientes apresentaram infecção pelo HHV-6 e 26 (86%) apresentaram infecção pelo CMV. Nove pacientes apresentaram encefalite após o transplante de fígado sendo que sete deles tiveram infecção pelo HHV-6 (p=0,0012), assim com o aumento da carga viral do HHV-6 se constatou a presença de encefalite após o transplante de fígado (p= 0.0226). O RT- PCR (p= 0,0306) para o CMV mostrou aumento significativo na segunda a quarta semana e décima a décima segunda semanas em relação aos outros testes, mostrando-se também mais sensível. Conclusão: concluímos que o aumento da carga viral do HHV-6 foi associado com a presença de encefalite após o transplante de fígado e a técnica de PCR em tempo real se mostrou como o teste mais sensível para detecção e monitorização do CMV nos pacientes transplantados de fígado
Abstract: Introduction: Opportunistic infections are a major problem for liver transplantation patients. Cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) are opportunistic common pathogens and HHV-6 has been associated with several disorders such as encephalitis. Real-time PCR (RT-PCR) is the gold standard for diagnosis of herpesvirus, as it has better accuracy, higher efficiency and less risk of contamination compared to other conventional tests. Objective: The aim of study was to evaluate the viral kinetics of HHV-6 and CMV by RT-PCR in patients undergoing liver transplantation and correlated with the presence of encephalitis complications occurring in the post-transplant period. Methods: We prospectively analyzed by RT-PCR the viral load of CMV and HHV-6 in 30 liver transplant patients. Monitoring of patients was performed prospectively from pretransplant (immediately before surgery-day zero) with donor and recipient samples and posttransplant: 2nd, 3rd, 4th, 6th, 8th, 10th and 12th weeks with a total of 270 serum samples. The protocol was followed according to the requirements for research and was approved by the Ethics Research Committee of the Faculty of Medical Sciences State University of Campinas (CEP nº 430/2003). The clinical findings were obtained from the medical records. For detection and quantification of DNA of the CMV and HHV-6 virus the commercial kits "Real- CMV Quant TM" and "HHV-6 Real -TM Quant" were used. Nested-PCR and antigenemia tests were performed routinely for CMV virus and their results obtained electronically. Statistical analysis comparing categorical variables was applied using Fisher exact test. To identify associated factors with increased viral load the method of Generalized Estimation Equation (GEE) and the accuracy and precision was used. Results: Thirteen (43 %) of the thirty patients had HHV-6; 26 (86 %) had CMV infection. Nine patients had encephalitis after liver transplantation and seven of them had HHV-6 (p = 0.0012) and with an increasing viral load of HHV-6 the presence of encephalitis after liver transplantation was found (p = 0.0226). RT-PCR (P = 0.0306 ) CMV showed a significant increase at the 2nd to 4th week and 10th to 12th week compared to the other tests, having also more sensibility. Conclusion: We concluded that the increase in viral load of HHV-6 was associated with the presence of encephalitis after liver transplantation and the technique of real-time PCR was shown to be the best sensibility test for the detection and monitoring of CMV in our liver transplant patient
Doutorado
Fisiopatologia Cirúrgica
Doutora em Ciências da Cirurgia
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28

Silva, Ana Carolina Guardia da 1980. "Detecção do DNA viral dos herpesvirus 5 e 6 em biopsias hepaticas de transplantados de figado." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311917.

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Orientador: Sandra Cecilia Botelho Costa
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: O Citomegalovírus (CMV) e o Herpesvírus humano 6 são vírus universais pertencentes à subfamília dos betaherpesvírus. Esses vírus permanecem latentes, podendo ser reativados por um período de imunossupressão, como acontece em pacientes submetidos a transplantes de fígado. O CMV é um importante patógeno oportunista, que influencia negativamente esses pacientes. O HHV-6 é um vírus linfotrópico, alem de infectar outras células como monócitos e células endoteliais, usando o receptor celular CD-46. A reativação do HHV-6 tem sido associada com a do CMV e rejeição do enxerto. Nos transplantados de fígado a reativação do HHV-6 tem aparecido junto com a infecção do CMV. O CMV tem sido associado como importante causa de mortalidade e morbidade nos transplantados de órgãos sólidos. Esses vírus podem causar disfunção no enxerto, supressão da medula e pré-disposição para a doença por CMV. Este estudo detectou o DNA do CMV e HHV-6 em 41 transplantados de fígado usando a Nested- PCR. Este método foi escolhido por ser mais sensível e possibilitar a genotipagem. Também analisamos a co-infecção e o impacto clínico desses vírus nos transplantados hepáticos. 145 biópsias foram analisadas (41 - biópsias de doador e 104 - biópsias pós-transplante). 23 (15.8%) das 145 foram positivas para o CMV e 53 (36.5%) positivas para o HHV-6. 19 (13%) tiveram a co-infecção na mesma amostra. 21 pacientes tiveram rejeição ao enxerto e desses 16 tiveram infecção viral. A presença desses vírus observado, nas biópsias hepáticas dos doadores e no pós- transplante, sugere que as infecções no pré-transplante são importante via de transmissão desses vírus aos receptores, causando episódios de rejeição.
Abstract: Cytomegalovirus (CMV), Human Herpesvirus-6 (HHV-6), belong to the ß-herpesvirus subfamily. These viruses can be reactivated from latency during immunosuppression. period especially after liver transplantation, CMV has been the most important opportunistc infection that negatively influences the outcome of patients. HHV-6 is a lymphotropic virus, but it may also infect other cells, such as monocytes and epithelial cells, using the CD46-molecule as a cellular receptor. HHV-6 reactivations are often seen associated with CMV infection and allograft rejection. In liver transplant patients, HHV-6 reativations are frequently found together with CMV infection. CMV has been implicated as an important causes of morbidity and mortality among solid organ transplant patients. Both have been related to graft dysfunction, bone morrow suppression, and predisposition to CMV disease. In this study, CMV and HHV-6 DNA were detected in 41 liver transplant patients, using nested polymerase chain reaction (PCR). This method was chosen because increase the sensibility and with the products we can be classified into CMV genotypes. We also evaluate the co-infection and the clinical impact between those virus in liver transplant patients. 145 biopsies were tested, (41 - liver donor biopsies and 104 - liver post- transplant), Twenty three (15,8%) of 145 liver biopsies were CMV- PCR positive and fifty three (36,5%) of 145 were positive HHV-6- PCR. Nineteen (13%) of 145 biopsies were both CMV and HHV-6 positive. 21 patients had allograft rejection and 16 had infection for this virus. With the presence of the viruses observed in the samples of the donor and post-transplant, suggests that pre-transplant HHV-6 and CMV infection may be a risk factor post-transplant. They had associated with allograft refection.
Mestrado
Mestre em Farmacologia
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29

Nitsche, Andreas. "Einfluss des Humanen-Herpesvirus 6 (HHV-6) auf die humane Chimären-Hämatopoese im Xeno-Transplantatmodell der NOD-SCID-Maus." [S.l.] : [s.n.], 2001. http://www.diss.fu-berlin.de/2001/207/index.html.

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30

Wallaschek, Nina [Verfasser]. "Role of the herpesvirus telomeric repeats and the protein U94 in human herpesvirus 6 integration / Nina Wallaschek." Berlin : Freie Universität Berlin, 2016. http://d-nb.info/110293318X/34.

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31

Telford, Marco 1984. "Genetic diversity and geographic patterns of human herpesvirus 4 and 6." Doctoral thesis, Universitat Pompeu Fabra, 2017. http://hdl.handle.net/10803/664509.

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This thesis focuses on Human herpesvirus 4 and 6, two ubiquitous viruses with a long list of putative disease associations, ranging from malignancies such as lymphomas and carcinomas to multiple sclerosis. To date, the relatively limited genetic data on these organisms hinders the understanding of their variability and their genetic structure at a population level. We here explore wet lab techniques for the production of genetic data in a cost-effective manner in order to reach the order of magnitude that is required to unravel the genetics these viruses. After successfully identifying individuals affected by integrated chromosomally inherited human herpesvirus 6 from public datasets of sequencing data, the sequences of the infecting virus were produced by target enrichment means from the source biological sample. The testing of an in-house target enrichment protocol followed, aiming to target latently infecting virus in human saliva. While the protocol still needs optimization and the aid of alternative techniques to be suitable for cost-effective, large-scale studies, the results were very satisfactory (up to >800-fold enrichment). In parallel, long range PCRs were used to produce human herpesvirus 4 latency genes sequences from one large human healthy saliva panel including populations previously unexplored in terms of human herpesvirus 4 isolates. Thanks to the combination of wet lab techniques and data analysis, the presence of genetic patterns in the two studied viruses is emerging, with human herpesvirus 6 presenting differences in diversity between its two species, as well as signs of geographical patterns possibly in part hidden by recombination events. Different bioinformatics approaches showed instead a stronger geographical stratification in human herpesvirus 4, with regional-driven clades. This information would allow us for a correct study design when addressing the relationship between virus and disease, taking into account the natural variation of the virus, as well as help to pinpoint genetic features that might be determinant for disease triggering or development. The strong geographical patterns presented by the diseases associated to these viruses strengthen the notion of the importance of this investigation and opens an avenue of research focused on disclosing the putative relationship between viruses strain variation and the risk for these virus–associated diseases.
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32

Parry, Christopher Marc. "Molecular identification, characterisation and processing of the Human Herpesvirus-6 Protease." Thesis, London School of Hygiene and Tropical Medicine (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.557278.

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33

Silva, Amanda Perse da. "Desenvolvimento de métodos de diagnóstico, silenciamento gênico e caracterização molecular do vírus herpes simples tipo 1 e herpesvírus humano tipo 6 em pacientes imunocomprometidos do Rio de Janeiro." reponame:Repositório Institucional da FIOCRUZ, 2015. https://www.arca.fiocruz.br/handle/icict/13045.

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Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil
A família Herpesviridae abriga um grande número de vírus que infectam animais e o homem. Nove herpesvirus foram identificados que possuem o homem como hospedeiro primário e descritos através da análise filogenética foram classificados em três subfamília: Alfaherpesvirinae, Betaherpesvirinae e Gamaherpesvirinae. A família Herpesviridae agrupa vírus de genoma DNA e que estão associados a infecções latentes e a manifestações clínicas recorrentes. As infecções por herpesvírus podem se manifestar de forma assintomática ou sintomática, podendo causar diferentes síndromes clínicas. Estes vírus normalmente são benigno, sendo o aparecimento de lesões nas mucosas a forma mais comum da doença, podendo causar doenças neurológicas severas principalmente em pacientes imunocomprometidos. A incidência e severidade podem ser exacerbadas entre indivíduos imunocomprometidos. A presente tese é composta por três manuscritos, sendo dois trabalhos publicados e um submetido. Estes estudos se propuseram a padronizar métodos de silenciamento gênico, otimizar e comparar métodos para o diagnóstico e realizar a caracterização genotípica do herpes simples tipo 1 (HSV-1) e herpesvírus humano tipo 6 (HHV-6). Os estudos foram realizados em paciente imunocomprometidos do estado do Rio de Janeiro No primeiro artigo \201CRNA interference inhibits herpes simplex vírus type 1 isolated from saliva samples and mucocutaneos lesions\201D, foi possível realizar a comparação da sensibilidade para detecção do HSV-1 por isolamento viral e pela metodologia da reação de PCR em tempo real em amostras de lesão, saliva e cultura celular . Além disso, neste estudo foi possível obter-se a inibição de mais 99% da replicação viral do HSV-1 in vitro utilizando a técnica de RNA de interferência. No segundo estudo \201CGenotypic characterization of herpes simplex vírus type 1 isolates in immucompromised patients from Rio de Janeiro, Brazil\201D realizamos a primeira caracterização genotípica do HSV-1 no Rio de Janeiro. Os resultados demonstraram a existência de um único genótipo viral circulando nas amostras de pacientes imunocomprometidos. Além disso, as amostras brasileiras apresentam um alto grau de identidade estamos agrupadas no mesmo clado. No terceiro artigo \201CAcute liver failure in an immunocompetent patient\201D, foi possível a detecção do HHV-6B no soro e no fígado de paciente com hepatite fulminante. Neste estudo, foi possível mostrar a contribuição do HHV-6B na hepatite aguda fulminante sem etiologia definida. Esses estudos contribuem para o conhecimento das características clínicas e genéticas do HSV-1 e do HHV-6 circulantes em pacientes imunocomprometidos do Rio de Janeiro, Brasil
The Herpesviridae family has a la rge number of virus widespread in animal s and human . Nine herpesvirus a re identified that have hum a ns as their primary host and described by phylogenetic analysis were classified into three subfamily : Alfaherpesvirinae, Betaherpesvirinae and Gammaherpesvirinae. The family Herpesviridae is family of DNA virus and that are associated with latent infections and recurrent clinical manifestations. Herpesvirus infections can manifest themselves in asymptomatic or symptomatic form, may cause different clinical syndromes. These viruses are usually benign and the appearance of mucosal lesions are more common, but severe neur ological diseases can occurred especially in immunocompromised patients. The incidence and severity may be exacerbated among immunoc ompromised individuals. This thesis consists o f three manuscripts, two published papers and submitted. These studies set out to standardize methods of gene silencing, optimize and compare methods for the diagnosis and the genotypic characterization of herpes simplex type 1 (HSV - 1) and human herpesviru s type 6 (HHV - 6). The studies were conducted in immunocompromised patient Rio de Janeiro. In the first article "RNA interference inhibits herpes simplex virus type 1 isolated from saliva samples and mucocutaneous lesions", the comparison of sensitivity for detection of HSV - 1 for viral isolation and PCR methodology in real time is possible for different types of samples. Furthermore, in this study it was possible to obtain the most 99% inhibition of viral replication of HSV - 1 in vitro using RNA interference technique. In the second study "Genotypic characterization of herpes simplex virus type 1 isola tes in immucompromised patients from Rio de Janeiro, Brazil" held the first genotypic characterization of HSV - 1 in Rio de Janeiro. The results demons trated the existence of a unique viral genotype circulating in the samples of immunocompromised patients. Furthermore, viruses of the isolates show a high degree of identity and form a single clade. In the third article "Acute liver failure in an immunocompetent pati ent," HHV - 6B detection in serum and liver of patients with fulminant hepatitis was possible. In this study, we show the HHV - 6B contribution to acute fulminant hepatitis of unknown etiology. These studies contribute to the kn owledge of clinical and genetic HSV - 1 and HHV - 6 circulating in immunocompromised patients in Rio de Janeiro, Brazil.
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34

Enbom, Malin. "Pathogenesis of the recently identified human herpesviruses 6 and 8 /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4405-9/.

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35

Clark, David J. "Identification of specificity determinants of Human Herpesvirus 6 chemokines and relations to immunotherapy." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.557266.

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36

Tsao, E. H. F. "Gene expression studies of lytic infection and chromosomal integration of human herpesvirus 6." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1445129/.

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Human herpesvirus 6 (HHV-6) was discovered in 1986 in patients with lymphoproliferative diseases and it has a predominant tropism for CD4+ T cells in vitro and in vivo. The virus can be divided into two variants: HHV-6A and 6B, based on the differences in biological properties and DNA sequences. HHV-6B has been shown to be the causative agent of exanthem subitum while HHV-6A has no clear association with any disease yet. The genome for both variants has been defined and each encodes just over 100 open readings frames (ORFs). However, there is limited knowledge regarding the functions and transcription kinetics of most ORFs. This thesis discusses the development of DNA microarrays for HHV-6 and the application of the arrays to characterise HHV-6B gene expression in the SupT1 cell line. The expression pattern of individual viral genes over a 60h time course (<1 replication cycle) was profiled. Viral genes were further classified into three kinetic groups: immediately-early (IE), early (E), and late (L), according to their transcriptional activity in the absence of de novo protein synthesis or DNA replication. In addition, HHV-6 presents an atypical stage in the herpesvirus life cycle in which the viral genome is integrated into host chromosomes. The prevalence of HHV-6 integration was estimated to be between 0.21% to 3%. An individual harbouring integrated HHV-6 was previously identified. The molecular biology and gene expression of this integrated HHV-6 DNA were characterised. Expression of viral genes belonging to all three kinetic classes (IE, E, and L) was detected in vitro and ex vivo. The data strongly suggest that the chromosomal HHV-6 sequence is transcriptionally active and the implications of this are discussed.
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37

Dahl, Helena. "Epidemiology and pathogenesis of HHV-6 /." Stockholm : [Karolinska institutets bibl.], 2002. http://diss.kib.ki.se/2002/91-7349-100-4/.

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38

Tait, Andrew Robert. "Isolation and characterization of recombinant U24, a membrane protein from human herpesvirus type 6." Thesis, University of British Columbia, 2011. http://hdl.handle.net/2429/36585.

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This thesis describes the isolation and characterization of the U24 membrane protein encoded by Human Herpesvirus type-6 (HHV-6), obtained from an E. coli recombinant expression system. HHV-6 infection has been previously associated with the disease multiple sclerosis (MS), and the U24 protein is of interest because it has a seven amino-acid sequence (PRTPPPS) identical to myelin basic protein (MyBP), a candidate auto-antigen in MS. In the first part of this thesis, I describe the methods that were developed to enable milligram quantities of U24 to be isolated and purified from litre cultures of E. coli. Levels of U24 expressed with a maltose binding protein-hexahistidine fusion tag were particularly enhanced by combinations of low temperature, oxidizing conditions, and/or use of minimal media culture. The significance of these results may be considered useful in application to other difficult-to-obtain membrane proteins. Subsequent chapters of this thesis describe testing the recombinant U24 for potential mimicry of MyBP structure and function. Since the polyproline region in MyBP is now being recognized for its potential in cell-signalling roles that relate to myelin sheath development and structural integrity, I hypothesized that U24 may retain some of the same attributes as MyBP on the basis of identical sequence. Results here suggest that U24 can adopt a polyproline type II helix much like MyBP, which is a structural feature important for engaging in protein-protein interactions. Furthermore, the region is also found to represent a PX(T/S)P MAPK phosphorylation motif and PXXP-based Fyn tyrosine kinase SH3 binding domain. These observations are of particular relevance since phosphorylated MyBP is particularly decreased in MS patients, and Fyn is critical to myelin development. Like MyBP, results suggest that U24 can be phosphorylated at the equivalent threonine and is also able to bind to the Fyn-SH3 domain. These results support the possibility that U24 interferes with essential myelin regulation pathways on the basis of its sequence shared with MyBP, thereby contributing to a pathological process. I conclude with a presentation of preliminary NMR structural data for U24, as well as review results from a study of U24 in an animal model system. Future directions are also discussed.
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39

Coyle, Peter Valentine. "Development and application of serodiagnostic assays for the investigation of human herpesvirus 6 infection." Thesis, Queen's University Belfast, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333774.

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40

Dewin, David Robert. "Characterisation of the human herpesvirus-6 U83A chemokine and application to infection and vaccines." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414774.

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41

Lopes, Amanda de Oliveira. "Prevalência das infecções causadas por herpesvírus humanos em portadores do HIV através de diagnóstico diferencial." reponame:Repositório Institucional da FIOCRUZ, 2016. http://www.arca.fiocruz.br/handle/icict/15119.

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Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil
Os herpesvírus humanos (HHV) (herpes simples 1 e 2, varicella-zoster, Epstein-Barr, citomegalovírus humano, herpesvírus humanos 6A, 6B, 7 e 8) estão associados à diversas doenças, porém são nos indivíduos portadores do vírus da imunodeficiência humana (HIV) que estes herpesvírus causam infecção grave e duradoura, podendo levá-los ao óbito. Contudo, no Brasil, pouco é conhecido sobre a verdadeira prevalência das infecções causadas por HHV nesses indivíduos devido a poucos estudos realizados no país. Portanto, este trabalho visou determinar a prevalência desta co-infecção HIV/Herpesvírus humanos através de um diagnóstico diferencial que detecta simultaneamente as nove espécieis de HHV (Pan-herpesvírus). Este método é baseado na amplificação, por reação em cadeia da polimerase (PCR) Nested, de uma região altamente conservada (DPOL) do genoma desses vírus e na identificação da espécie viral por sequenciamento do genoma viral. Além disso, este estudo visou avaliar possíveis fatores associados com a prevalência desta co-infecção, como sexo, idade e taxas de linfócitos T CD4+ (LT CD4+), e destinou-se comparar a prevalência das infecções causadas por HHV entre indivíduos HIV reagentes (grupo teste) e indivíduos não reagentes para este vírus (grupo controle). Para isso, 241 amostras de soro de indivíduos portadores do HIV coletadas durante os anos de 2012 (95 amostras), 2013 (89 amostras) e 2014 (57 amostras), e 94 amostras de soro de indivíduos HIV não reagentes coletadas durante o ano de 2013 foram testadas através de PCR Nested As amostras amplificadas foram sequenciadas para a identificação da espécie viral. Com isso, neste estudo foi encontrada prevalência da co-infecção HIV/HHV de 14,1% (34/241), sendo 13% (31/241), 0,8% (2/241) e 0,4% (1/241) relacionado às co-infecções HIV/HSV-1, HIV/HHV-6 e HIV/HHV-8, respectivamente. Também foi observada diminuição estatisticamente significativa (p-valor < 0,0001) da prevalência da co-infecção HIV/HHV durante os anos estudados. Já o grupo controle obteve menor prevalência da infecção causada por HHV (1,1%; 1/94) e foi referente à infecção causada por HHV-6. Ademais, foi verificada associação estatisticamente significativa da detecção da co-infecção HIV/HSV-1 com as taxas de LT CD4+, evidenciando que a taxa LT CD4+ <500 células/mm³ é um fator de risco para infecções causadas por HSV-1 em indivíduos HIV reagentes (p-valor < 0,0327/ p-valor <0,0186). A partir disto, foi verificado que o Pan-herpesvírus foi eficiente na detecção das co-infecções HIV/HSV-1, HIV/HHV-6 e HIV/HHV-8. Sendo assim, este trabalho contribuiu para a investigação da prevalência das infecções causadas por herpesvírus humanos em indivíduos HIV reagentes no Rio de Janeiro/Brasil
The human herpesviruses (HHV) (herpes simplex 1 and 2, varicella-zoster, Epstein-Barr virus, human cytomegalovirus, human herpesviruses 6A, 6B, 7 and 8) are associated with several diseases, but these herpesviruses cause serious and lasting infection in individuals infected by the human immunodeficiency virus (HIV) and can lead to death. However, in Brazil few is known about the true prevalence of human herpesviruses infection in these individuals because of few studies in the country. Therefore, this study aimed to determine the prevalence of co-infection HIV/human herpesviruses through a differential diagnosis that simultaneously detects nine HHV species (Pan-herpesviruses). This method is based on amplification a highly conserved region (DPOL) genome of these viruses by Nested polymerase chain reaction (PCR) and on viral species identification by sequencing of the viral genome. In addition, this study aimed to evaluate possible factors associated with the prevalence of co-infection, such as sex, age and T CD4+ lymphocytes rates (LT CD4+), and aimed to compare the prevalence of infections caused by HHV among individuals HIV reagents and no reagents for this virus (control group). For this, 241 serum samples from individuals with HIV collected during the years 2012 (95 samples), 2013 (89 samples) and 2014 (57 samples), and 94 serum samples from individuals without HIV collected during the year 2013 were tested by Nested PCR The amplified samples were sequenced for identification of the viral species. This study found prevalence of co-infection HIV/HHV 14,1% (34/241), in which 13% (31/241), 0,8% (2/241) and 0,4% (1/241) were related with the co-infections HIV/HSV-1, HIV/HHV-6 and HIV/HHV-8, respectively. A decrease statistically significant (p-value <0,0001) in the prevalence of co-infection HIV/HHV was observed during the years of study. The control group had lower prevalence of infection caused by HHV (1,1%; 1/94) and was related with the infection caused by HHV-6. In addition, there was a statistically significant association between detection of co-infection HIV/HSV-1 with LT CD4+ rates, showing that LT CD4+ rate <500 cells/mm³ is a risk factor for infections caused by HSV-1 in individuals HIV reagents (p-value <0,0327 / p-value <0,0186). From this, was verified that the Pan-herpesviruses was efficient in the detection of co-infections HIV/HSV-1, HIV/HHV-6 and HIV/HHV-8. Therefore, this study contributed to the investigation of the prevalence of infections caused by human herpesviruses in people living with HIV in Rio de Janeiro/Brazil
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42

Peigo, Murilo de Freitas 1987. "Infecção ativa por herpesvírus em pacientes com lúpus eritematoso sistêmico (LES)." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311946.

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Orientadores: Sandra Cecília Botelho Costa, Sandra Helena Alves Bonon
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: O Lúpus Eritematoso Sistêmico (LES) é uma patologia sistêmica do tecido conjuntivo, que se apresenta de maneira variada na dependência do órgão afetado, da gravidade de seu acometimento e da idade do paciente, tendo influência de fatores raciais, de padrões imunológicos e ambientais. Pacientes lúpicos têm grande predisposição para desenvolver infecções graças à imunossupressão induzida pela própria doença como pelo uso de vários medicamentos em seu tratamento. Infecções causadas por herpesvírus, principalmente o Citomegalovírus Humano (CMV) e o Epstein-Barr (EBV), têm sido implicadas em várias doenças autoimunes graves, incluindo o LES. A reativação dos herpesvírus 6 e 7 (HHV-6 e HHV-7) geralmente ocorre em pacientes imunodeprimidos, mas seus papéis ainda são pouco estudados. As infecções por herpesvírus têm influência tanto no início do processo autoimune quanto na exacerbação da progressão da doença. A identificação de pacientes com alto risco de desenvolver doença pelos herpesvírus pode ser realizada utilizando técnicas de detecção de infecção ativa, como a Reação em Cadeia da Polimerase (Nested-PCR) e a detecção do antígeno pp65 do CMV (Antigenemia). Dependendo do caso, estes pacientes podem receber tratamento com antivirais. Diante do exposto, os objetivos deste estudo foram: monitorizar os pacientes com LES em relação à infecção ativa por CMV, EBV, HHV-6 e HHV-7, utilizando as técnicas de Nested-PCR e de antigenemia, bem como avaliar o impacto clínico dessas infecções. Foram incluídos neste trabalho, amostras de sangue de 71 pacientes em seguimento no Departamento de Reumatologia da Faculdade de Ciências Médicas ¿ UNICAMP, com diagnóstico de LES confirmado, sendo que 20/71 (28%) estavam com o lúpus ativo (SLEDAI ? 8) e 51/71 (72%) dos pacientes não tinham atividade lúpica (SLEDAI < 8). Das amostras de sangue pesquisadas, 10/71 (14%) foram positivas para os herpesvírus estudados, sendo que 90% destes pacientes com infecção ativa apresentavam o lúpus em atividade (p?0,006). Infecção ativa pelo CMV ocorreu em 4 pacientes (5,6%). HHV-7 foi detectado em 4 amostras (5,6%). Dois outros pacientes apresentaram dupla infecção por CMV e HHV-7 (2,8%). Infecção ativa pelo EBV e HHV-6 não foi detectada em nenhuma das amostras analisadas. Dois pacientes foram a óbito, sendo que um deles evoluiu com sepse de foco pulmonar (provável doença por CMV) e o outro com sepse por Psedomonas aeruginosa. Diante dos resultados obtidos, podemos observar que a infecção ativa pode ocorrer nos pacientes com LES, principalmente naqueles com a doença em atividade. Poucos estudos têm avaliado o impacto destas infecções no cuidado diário dos pacientes com LES. Acreditamos que este trabalho seja pioneiro e será de fundamental importância, contribuindo com este grupo de pacientes. Entretanto, futuros estudos deverão ser implementados com um número maior de pacientes e de coletas/paciente, principalmente naqueles com LES em atividade, que foram demonstrados com aqueles com fator de risco aumentado
Abstract: Systemic lupus erythematosus (SLE) is a connective tissue systemic pathology that presents itself in several ways, depending on the organ affected, the seriousness of the disease and patient¿s age, being influenced by racial factors, immunologic and environmental patterns. SLE patients have great predisposition to develop infections due to the immunosuppression induced by the disease itself and by the use of medicine in the treatment. Infections caused by herpesvirus, especially Human Cytomegalovirus (CMV) and Epstein-Barr (EBV), have been developed into several serious autoimmune diseases, including SLE. Herpesvirus 6 and 7 (HHV-6 and HHV-7) reactivation generally occurs in immunodepressed patients, but their roles are unclear. Herpesvirus infections have influence both on the beginning of the autoimmune process and on the aggravation of the disease progression. The patients that present high risks of developing herpesvirus related diseases can be identified using active infection detection techniques, such as the Nested polymerase chain reaction (Nested-PCR) and the CMV pp65 antigen detection (antigenemia). Depending on the case, the patients can receive treatment with antivirals. Face to the exposed, the objectives of this study were: to monitor the patients with SLE with regard to active infection by CMV using Nested-PCR and antigenemia techniques, and EBV, HHV-6, HHV-7 in serum, as well as to evaluate the clinic impact to these infections. There were included in this work blood samples of 71 patients that are being treated at the Department of Rheumatology, Faculty of Medical Sciences ¿ University of Campinas - UNICAMP, with a confirmed SLE diagnosis, given that 20/71 (28%) had active lupus (SLEDAI ? 8) and 51/71 (72%) of the patients didn¿t present lupic activity (SLEDAI < 8). Considering the blood samples researched, 10/71 (14%) were positive for the studied herpesvirus, and 90% of the patients with active infection presented lupus in activity (p ? 0,006). Active infection by CMV was observed in 4 patients (5,6%). HHV-7 was detected in 4 samples (5,6%). Two other patients presented double infection by CMV and HHV-7 (2,8%). Active infection by EBV and HHV-6 was not detected in any of the analyzed samples. Two patients have deceased, whose conditions developed into pulmonary sepsis (probable disease by CMV) and into Psedomonas aeruginosa sepsis, respectively. After analyzing the achieved results, we observe that active infection can appear in patients with SLE, especially in those with the disease in activity. Few studies have evaluated the impact of these infections on the daily care of patients with SLE. In this sense, we believe that this work is pioneer and that it will be of fundamental importance, contributing to this group of patients. However, future studies should be implemented, with a larger number of patients and samples, especially those with SLE in activity, which are the ones with increased risk factor as shown
Mestrado
Clinica Medica
Mestre em Clinica Medica
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43

Andreatta, Rafaela Manfro Rorato. "Pesquisa de herpesvírus 6 em amostras de tecido cerebral de pacientes submetidos à cirurgia como tratamento para epilepsia." Pontifícia Universidade Católica do Rio Grande do Sul, 2011. http://hdl.handle.net/10923/1285.

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Human herpesvirus 6 (HHV-6) is a Betaherpesvirus associated with Roseola Infantum (Exanthema Subitum) in primary infection. Due to its neurotropic characteristic and latency in the central nervous system, many reports associate HHV-6 with epilepsy, febrile seizures, multiple sclerosis and others neurologic diseases. In this study, HHV-6 DNA was investigated in 42 hippocampal samples from 14 patients with mesial temporal lobe epilepsy (MTLE) submitted to amygdalohippocampectomy (AH) or anterior temporal lobectomy (ATL) surgeries using a nested polymerase chain reaction (PCR). Three samples from each patient were collected and analyzed: from hippocampal head, body and tail. HHV-6 was detected in twelve of fourteen patients (85. 7%) with MTLE. Analyzing the samples resulting positive for HHV-6, all three samples were positive in three patients, in four patients two samples were positive and in five patients only one sample was positive. According to the origin of samples, seven samples from hippocampal head were positive, eight from hippocampal body and seven from hippocampal tail, showing no preferential site for viral establishment. HHV-6 positivity found in patients of the present study is higher then data found in the literature. A possible explanation would be differences in the study design, with three samples collected from each patient, which could be more representative than only one sample. Our results corroborate the hypothesis of a possible role of HHV-6 infection in epilepsy.
O Herpesvírus Humano tipo 6 (HHV-6) é um vírus da família Herpesviridae associado ao desenvolvimento de roséola infantil ou exantema súbito, doença caracterizada por febre alta, rash cutâneo e ocasionalmente convulsões febris. A prevalência mundial de infecção por HHV-6 é alta. Estima-se que cerca de 83% das crianças até 13 meses e mais de 95% das com idade até 2 anos já entraram em contato com o vírus. Existem duas variantes do HHV-6 já identificadas, as variantes A e B, sendo o HHV-6B o agente principal relacionado aos casos de roséola infantil. Epilepsia é um termo aplicado a um grupo de patologias crônicas caracterizadas, principalmente, pela ocorrência de crises epilépticas. As epilepsias representam em torno de 1% dos distúrbios neurológicos que afetam a população mundial. As crises são provocadas por uma disfunção da atividade elétrica cerebral associada a anormalidades estruturais e metabólicas causadas, em alguns casos, pela presença de vírus no sistema nervoso central. Por apresentar características como neurotropismo e latência no sistema nervoso central, procuramos relacionar o HHV-6 com a epilepsia do lobo temporal mesial (ELTM). Através de reação em cadeia da polimerase (PCR), pesquisamos a presença do vírus em 42 amostras de hipocampo de 14 pacientes com epilepsia do lobo temporal mesial (ELTM) submetidos a amígdalo-hipocampectomia (AH) ou lobectomia temporal anterior (LTA) como tratamento para a epilepsia. Três amostras de cada paciente foram analisadas: cabeça, corpo e cauda do hipocampo. O DNA do HHV-6 foi detectado em 12 dos 14 pacientes (85,7%) com ELTM. Três pacientes foram positivos em todas as três amostras, 4 pacientes foram positivos em duas amostras e 5 em apenas uma amostra. Com relação à origem das amostras, 7 foram positivas na cabeça do hipocampo, 8 no corpo do hipocampo e 7 na cauda do hipocampo, demonstrando não haver um sítio de preferência para o estabelecimento do vírus. A positividade para HHV-6 encontrada nos pacientes deste estudo é maior do que os dados encontrados na literatura. Uma possível explicação para esta elevada positividade poderia ser as diferenças na concepção do estudo, com três amostras coletadas de cada paciente, o que II pode ser mais representativo do que a coleta de apenas uma amostra. Nossos resultados reforçam a hipótese de um possível papel da infecção pelo HHV-6 na epilepsia.
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44

Heessen, Stijn. "Regulation of the ubiquitin-proteasome system : characterization of viral and cellular stabilization signals /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-600-6/.

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45

Pantry, Shara. "Persistent Infection with Human Herpesvirus-6 in Patients with an Inherited Form of the Virus: A Newly Described Disease." Scholar Commons, 2013. http://scholarcommons.usf.edu/etd/4928.

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Human Herpesvirus 6A (HHV-6A) and 6B (HHV-6B) are ubiquitous betaherpesviruses. Both viruses are associated with a variety of adult disorders including neurological disorder, such as multiple sclerosis and chronic fatigue syndrome. HHV-6 viruses are capable of establishing latency by integration into the telomeres of the host chromosome and are transmitted in a Mendelian manner in approximately one percent of the population. To date little is known about the immunological and neurological consequences of HHV-6 inheritance. This study focused on a unique population of individuals that inherited HHV-6 and present with chronic fatigue-like symptoms, including hypersomnia, generalized fatigue, headache, and short term and long term memory impairment. The central hypothesis of this study was that active replication of HHV-6 correlates with patient symptoms. To address this aim we first looked at the reactivation of integrated HHV-6 in vitro by inducing viral replication with epigenetic modifiers trichostatin A (TSA), valproic acid, sodium butyrate, and carbamazepine, and found TSA to be an effective method of inducing reactivation of HHV-6 from its integrated form. Additionally, a reactivated HHV-6A virus isolated from a patient with inherited HHV-6 was fully sequenced and the nucleotide and amino acid sequence was compared to that of fully sequenced HHV-6 laboratory strains, as well as the inherited virus. The reactivated virus was found to be very similar to the HHV-6A GS strain; however, there was some divergence at the right end of the viral genome and regions of the genome that do not contain herpesvirus core genes. Interestingly, the sequenced reactivated virus was found to differ from the HHV-6 virus which was inherited. Finally, HHV-6 replication was assessed by performing reverse transcriptase PCR assay for the viral glycoprotein U100 in patients receiving antiviral treatment. Results indicated that short term antiviral treatment was insufficient to abrogate viral replication, while treatment of six weeks or longer eliminated viral mRNA in patient blood samples. Furthermore, sequencing of the viral mRNA and inherited viral DNA indicate that the source of the mRNA detected in patient blood samples was an exogenously acquired HHV-6 virus, as the U100 glycoprotein sequences were not identical. Together these studies indicate that although HHV-6 can be reactivated from its integrated form, individuals in this unique population harbored an exogenous HHV-6 virus, in addition to the inherited virus; we termed this condition inherited herpesvirus syndrome. The fact that these individuals are able to acquire exogenous HHV-6 viruses suggest that there may be some level of immune tolerance or immune dysfunction; we suggest that further studies focus on uncovering the immune response to HHV-6 in individuals with an inherited form of the virus.
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46

Xu, Yunhe. "Molecular and diagnostic aspects of the protein p41 of HHV-6 and silencing of the CD46 receptor by RNA interference /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-553-0.

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47

Martin, Michelle Elizabeth Denny. "Physical and genetic characterization of the genome of human herpesvirus 6 strain U1102 : identification of immediate-early and regulatory genes." Thesis, Open University, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314868.

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48

Tanner, Anne. "Human Herpesvirus 6A Infection and Immunopathogenesis in Humanized Rag2-/-γc-/- Mice and Relevance to HIV/AIDS and Autoimmunity." BYU ScholarsArchive, 2016. https://scholarsarchive.byu.edu/etd/6078.

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Human herpesvirus 6A (HHV-6A) has yet to be definitively linked to a specific disease. This is due in part to the ubiquitous nature of the virus. Humanized Rag2-/-γc-/- (Rag-hu) mice were tested to determine if these were a suitable animal model to study the virus. Both cell-free and cell-associated virus was used for infection and both were found to be efficient at infecting the mice. Viral DNA was found in the plasma and cellular blood fractions, bone marrow, lymph node, and thymus, indicating successful infection and propagation of the virus in vivo. The CD3+CD4- population was depleted, while the CD3-CD4+ was increased in infected animals. The CD3-CD4+CD8- and CD3+CD4+CD8- populations were depleted and the CD3+CD4+CD8+ population increased when analysis was gated upon CD4+ cells. The CD3-CD4+CD8+ population expanded and the CD3-CD4+CD8- population was reduced when analysis was gated on the CD3- population. Additional flow cytometry analysis revealed increases in CD4+CD8+ double positive cells in the peripheral blood of cell-free infected mice, which could indicate improper T cell selection and a premature departure of these cells from the thymus, possibly contributing to autoimmunity. Previous research has shown that HIV and HHV-6A may have a synergistic effect on one another and that HHV-6A may act as a cofactor in the progression to AIDS. After determining the Rag-hu mouse model was suitable for studying HHV-6A infection, a coinfection of HHV-6A and HIV-1 was performed. Coinfected mice had fewer thymocytes when compared with the HIV-1 only, mock-infected, and to a lesser extent HHV-6A only groups which could indicate increased cell death in the coinfected group as well as possible disruptions in migration of cells, either causing cells to be sequestered in the bone marrow and unable to migrate to the thymus, or causing premature egress of the cells in the thymus due in part to premature upregulation of CCR7, both of which would explain the smaller cellular populations found in the coinfected mouse thymi. Additional studies were performed to determine if a preferential targeting existed between HHV-6A and HIV-1 as these viruses are found simultaneously coinfecting the same cell. Preferential targeting was not observed by cell-associated migration assay, but increased migration of HHV-6A-infected cells was observed in a CCL21 dependent manner. These studies have provided useful information about HHV-6A and its relevance to HIV/AIDS as well as a possible mechanism of the involvement of HHV-6A in multiple sclerosis (MS) and other autoimmune diseases.
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Gulve, Nitish [Verfasser], Thomas [Gutachter] Rudel, Joerg [Gutachter] Wischhusen, and Bhupesh [Gutachter] Prusty. "Subversion of Host Genome Integrity by Human Herpesvirus 6 and Chlamydia trachomatis / Nitish Gulve ; Gutachter: Thomas Rudel, Joerg Wischhusen, Bhupesh Prusty." Würzburg : Universität Würzburg, 2019. http://d-nb.info/1176411152/34.

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50

Hammarstedt, Maria. "Incorporation of cellular proteins into enveloped virus particles /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-966-1/.

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