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1

Görander, Staffan. "Functions of glycoprotein G of herpes simplex virus type 2." Göteborg : Dept. of Infectious Medicine, Section for Virology, Sahlgrenska Academy, 2010. http://hdl.handle.net/2077/21861.

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2

Teepe, Annette. "Relationship of Estrous Cycle to Herpes Simplex Virus Type 2 Susceptibility in Female Mice." Thesis, North Texas State University, 1987. https://digital.library.unt.edu/ark:/67531/metadc500408/.

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In CBA/NJ mice, splenic natural killer (NK) cell activity varies with stages of estrous. Susceptibility of ICR mice to intravaginal inoculation of herpes simplex virus type 2 (HSV-2) decreases with age. Susceptibility of female ICR and CBA/NJ mice to HSV-2 inoculated intravaginally and intraperitoneally was examined during the estrous cycle. In cycling ICR mice, greatest susceptibility to intravaginal inoculation was observed during diestrous and the least during metestrous. CBA/NJ mice were most susceptible to intravaginal inoculation of HSV-2 during diestrous. ICR mice were ovariectomized to mimic diestrous and found to be highly susceptible to intravaginal inoculation at all virus doses. No difference in susceptibility among phases of the estrous cycle was seen following intraperitoneal inoculation.
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3

Rajaguru, Suesha Chandani. "Inhibition of herpes simplex virus replication using small interfering rna that target icp4 gene of herpes simplex type 2." [Gainesville, Fla.] : University of Florida, 2004. http://purl.fcla.edu/fcla/etd/UFE0007066.

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Thesis (M.S.)--University of Florida, 2004.
Typescript. Title from title page of source document. Document formatted into pages; contains 65 pages. Includes Vita. Includes bibliographical references.
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4

Looker, Katharine Jane. "Viral antagonism : The role of herpes implex virus type 1 in the epidemiology and control of herpes simplex virus type 2." Thesis, Imperial College London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501080.

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5

Obasi, Angela I. N. "The epidemiology of herpes simplex virus type 2 infection in Mwanza region, Tanzania." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.536824.

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6

Chu, Yatson. "Herpes simplex virus type 2 regulates the IFN-gamma receptor expression and function." Thesis, University of Ottawa (Canada), 2003. http://hdl.handle.net/10393/26460.

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This study shows that HSV-2 can cause down-regulation in IFN-gammaR expression on the monocyte surface in both HSV-2 seropositive and seronegative patients. The objective of this work is to examine and explain the mechanisms involved in the viral down-regulation of IFN-gammaR. The first question I tried to answer was whether humoral factors might participate in this down-regulation. Humoral factors were not involved in this phenomenon. Next, cell-to-cell interactions were examined. T, B or natural killer cell depletion experiments were conducted in peripheral blood mononuclear cells of both HSV2 seropositive and seronegative patients. The results suggest that NK cells and T cells but not B cells were involved in the IFN-gammaR downregulation in HSV-2 seropositive patients. In addition, purified monocytes also demonstrated IFN-gammaR down-regulation after HSV-2 exposure in seropositive patients. I concluded that, in HSV-2 seropositive patients, NK cells may have an inhibitory effect and T cells may have a facilitatory role in the down-regulation of IFN-gammaR. (Abstract shortened by UMI.)
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7

Chatterjee, Somik. "STRUCTURE-FUNCTION ANALYSIS OF THE VIRULENCE PROTEIN ICP34.5 FROM HERPES SIMPLEX VIRUS TYPE 2." Kent State University / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=kent1248108386.

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8

Mbopi-Keou, Francois-Xavier. "The role of Herpes simplex virus type 2 (HSV-2) as a cofactor in HIV transmission." Thesis, Open University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247049.

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9

Thapa, Manoj. "Chemokines and chemokine receptors that mediate immune defense to genital herpes simplex virus type 2 (HSV-2) infection." Oklahoma City : [s.n.], 2008.

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10

Svensson, Alexandra. "Immune regulation of herpes simplex virus type 2 infection : special emphasis on the transcription Factor T-bet /." Göteborg : Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy, Göteborg University, 2006. http://hdl.handle.net/2077/852.

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11

Le, Goff Jérôme. "Interactions entre le VIH-1 et l' herpes simplex de type 2 dans le microenvironnement cellulaire et génital." Paris 7, 2005. http://www.theses.fr/2005PA077105.

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12

Wong, Kiing Aik. "Age related seroepidemiological survey of measles, mumps, rubella, varicella zoster, herpes simplex type 1 and 2 viruses." Thesis, University of Manchester, 2015. https://www.research.manchester.ac.uk/portal/en/theses/age-related-seroepidemiological-survey-of-measles-mumps-rubella-varicella-zoster-herpes-simplex-type-1-and-2-viruses(7188f535-e90e-4e18-a5cb-9b5ed1a75c68).html.

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Age stratified seroepidemiological studies play a crucial role in the design and assessment of vaccination strategies. An existing multiplex bead immunoassay for measles, mumps, rubella and varicella zoster virus antibodies together with a newly developed multiplex bead immunoassay for herpes simplex virus type 1 and type 2 antibodies were used to investigate the age-related seroepidemiology of these viruses in England during 2012.To develop the HSV-1 and HSV-2 antibody assay, attempts were made to produce full length of HSV-1 and HSV-2 glycoprotein G using a baculovirus vector expression system. While HSV-1 gG protein was produced, the proteins were extensively aggregated. Native glycoprotein G molecules undergo partial removal of HSV-1 signal sequence and HSV-1 short membrane anchor sequence during post translational modification. It is possible that such post translational modification is not performed when protein is processed in insect cell culture. Attempts to produce an HSV-2 glycoprotein G were not successful. It is possible that the high GC-content of HSV-2 glycoprotein G led to poor fidelity of copying the PCR amplification sequence. Commercially available truncated HSV-1 gG and HSV-2 gG were therefore used to develop a duplex microbead immunoassay for the simultaneous detection of specific HSV antibodies in human sera. The resultant assays performed with low sensitivity and specificity (HSV-1 of 89% and 66%, respectively and for HSV-2 of 79% and 85%, respectively) compared to the reference HerpeSelect ELISA.The MMRV multiplex bead immunoassay proved rapid, and required minimal sample volume to semi-quantify MMRV specific antibodies. The seroepidemiology of MMR results was compared with previous seroepidemiological studies performed in 1996 in England. The comparison showed an increase in the proportion of individuals who were positive for mumps and measles antibodies in the 2012 survey. The proportion of individuals positive for rubella was essentially unchanged. The increase in the proportion of individuals positive for mumps and measles antibodies in 2012 show the effectiveness of the change in MMR vaccination policy for England from 1996 onward. For VZV, the proportion of individuals who were positive for varicella antibodies between the 1996 and 2012 serological surveys were essentially unchanged. The comparison showed that most young children are susceptible to VZV. At this level of immunity, it can be expected that varicella will continue to produce epidemics of infection in the population, unless varicella vaccination is implemented as a part of routine childhood vaccination.
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13

Koch, Christine. "Antivirale Effekte ausgewählter ätherischer Öle auf behüllte Viren unter besonderer Berücksichtigung des Herpes simplex Virus Typ 1 und 2 /." [S.l. : s.n.], 2005. http://www.gbv.de/dms/bs/toc/511115164.pdf.

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14

Chatterjee, Koushik. "A study of host genetic determinants of human papillomavirus (HPV) infection, cervical cancer and herpes simplex virus type-2 (HSV-2) infection." Doctoral thesis, University of Cape Town, 2010. http://hdl.handle.net/11427/3160.

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15

Deka, Srilekha. "Induction of the Chlamydia trachomatis Persistent State by Herpes simplex Virus Type 2 Does Not Require Productive Viral Replication." Digital Commons @ East Tennessee State University, 2005. https://dc.etsu.edu/etd/1065.

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Clinical and epidemiological studies have shown that multiple infection with HSV-2 and Chlamydia trachomatis occurs in vivo. We hypothesize that (i) HSV-2 co-infection of C. trachomatis infected cervical epithelial cells induces chlamydial persistence; (ii) productive HSV-2 replication is required for induction of persistence in C. trachomatis; (iii) co-infection with C. trachomatis and HSV-2 alters accumulation of immuno-modulatory molecules in infected cells. To test these hypotheses, a cell culture model of co-infection was established in HeLa cells. Transmission electron microscopic (TEM) analyses demonstrated aberrant chlamydial morphology in co-infected cells, which was apparent by 10 hours and prominent by 20 hours post HSV-2 infection. Moreover, co-infection reduced infectivity of progeny chlamydiae. These observations indicate chlamydial persistence and are consistent with certain historical 'markers' of persistence previously described. Since chlamydial persistence was being established, we were interested in unraveling the mechanism of induction. To determine whether HSV-2 replication was necessary, cyclohexamide (Cx), a eukaryotic protein synthesis inhibitor, was used. Cx inhibits host cell and viral protein synthesis by >95% and productive viral replication by >90%. Development of chlamydial persistence was observed in the presence of Cx. To analyze whether events during attachment and entry are sufficient for induction of chlamydial persistence, UV-inactivated, replication incompetent HSV-2 (HSV-2uv) was used. HSV-2uv is capable of attachment and entry but incapable of productive replication. Chlamydial persistence also developed during co-infection with C. trachomatis and HSV-2uv. Both of these observations suggest that an early event/s in HSV-2 replication, most probably occurring during HSV-2 attachment and entry, is sufficient for induction of chalmydial persistence. These observations also suggest that productive viral replication is not required for the induction of chlamydial persistence. Accumulation of chlamydial major outer membrane (MOMP) was decreased whereas pro-inflammatory chlamydial heat shock protein 60 (cHSP60) was increased in co-infected cells compared to C. trachomatis singly-infected cells. Among the cytokines looked at, an elevation in the levels of IL-6 was observed in HSV-2 infected and co-infected samples. Release of chlamydial antigens during chlamydial persistence increases inflammation and disease severity in vivo. Therefore, co-infection might increase immunopathology compared to that observed in C. trachomatis singly-infected individuals.
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16

Freeman, Esther. "The role of herpes simplex virus Type 2 in the spread and control of HIV in four Sub-Saharan African Cities." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.429308.

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17

Biraro, Samuel. "Herpes simplex virus type-2 : epidemiological trends and relation with trends in HIV incidence and HIV transmission in south western Uganda." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.549766.

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18

Hu, Nai-Chung. "Co-occurrence of shedding Herpes Simplex Virus type-2 (HSV-2), Human Papilloma Virus (HPV) and Human Immunodeficiency Virus 1 (HIV-1) in the female genital tract among HIV-infected women." Master's thesis, Faculty of Health Sciences, 2019. http://hdl.handle.net/11427/31250.

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Introduction: Human Immunodeficiency Virus remains as one of the largest pandemics in the world, with the prevalence of more than 70% of HIV-infected individual reside in Sub-Saharan Africa. Moreover, other sexually transmitted viral infection such as Human Papillomavirus and Herpes Simplex Virus also show a high prevalence in Sub-Saharan Africa. Recent studies show the presence of other viral STI in the genital region may have increased HIV shedding in the genital region. However, it not clearly known if the presence of ART or HIV may affect the shedding of other viral STI in the genital region and if the combination of other viral STI treatment and ART is necessary to treat an individual with multiple STI infection. Methods: This is a secondary data analysis study, based on analysing the data collected from a single-site, double-blinded randomized control study (2-IUD study). The research site was the Gugulethu Community Health Centre, Cape Town, South Africa and samples were collected between 2014 and 2018. Analysis was conducted on genital tract specimens of study participants obtained via the Menstrual Cup (MC) and Endocervical Swabs (ECS), collected at baseline, 3 and 6 months’ follow up visit from randomly selected 52 ART-Naïve participants and 56 age-matched women from the ART-Using group of the primary study. Logistic regression models were constructed to measure the associations between possible risk factors and viral STIs. Results are presented as odds ratios (OR) with 95% confidence intervals (CI). Results: ART-Naïve women had higher rates of HIV shedding in the genital tract at each visit. However, more than half of women using ART, most of them virally suppressed, had detectable genital HIV at one or more visits. Most of the participants showed pre-exposure to HSV-2, but shedding of HSV-2 was substantially less common. HPV was detected in 72% of the participants, with no significant difference by ART status. Overall, 70.3% of samples had at least one viral pathogen detected - 60.4% among ART-Using women compared to 82.8% in ART-Naïve women (P<0.001). Compared to ART-Naïve women, ART-Using women were significantly less likely to have co-occurrence of viral shedding overall. However, ART-Using women with higher VL had levels of viral co-occurrence similar to those of ART-Naïve women. Conclusion: Our analysis demonstrated that the ART-Using women were less likely to shed HIV, HSV-2, HPV and viral STI co-infection in the genital tract compared to ART-Naïve women. This may be be driven by plasma VL levels where ART-Using women with lower VL are less likely to shed these viruses compared to women with elevated VL, including those not on ART.
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19

Burrel, Sonia. "Virus herpes simplex de type 2 : développement de nouveaux outils d’investigation des mécanismes moléculaires de la résistance aux antiviraux et de la diversité génétique." Paris 6, 2013. http://www.theses.fr/2013PA066451.

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Au cours de ce travail, la résistance génotypique du virus herpes simplex de type 2 (HSV-2) a été étudiée. Initialement, nous avons mis en évidence un faible polymorphisme naturel, sans conséquence sur la sensibilité aux antiviraux, de la thymidine kinase (TK, gène UL23) et du complexe ADN polymérase/facteur de processivité (gènes UL30 et UL42). Dans le but de démontrer l’implication dans la résistance à l’aciclovir (ACV) de nouvelles mutations identifiées dans la TK, nous avons mis au point une méthode d’étude de l’activité de phosphorylation de l’ACV in vitro par des TK recombinantes. L’objectif de ces travaux était de mettre au point une méthode générale de détection de la résistance des HSV aux antiviraux fondée uniquement sur l’analyse génétique. Un test de résistance génotypique a mis en évidence une variabilité anormalement élevée du gène UL30 d’un isolat clinique de HSV-2. Le criblage rétrospectif des souches cliniques par un système spécifique de PCR en temps réel, a permis d’estimer la prévalence de ce nouveau variant de HSV-2 variant (HSV-2v) à 3%. Les patients infectés étaient tous originaires d’Afrique sub-saharienne et fréquemment co-infectés par le HIV. Sur l’arbre phylogénique construit à partir des séquences UL30, ces isolats de HSV-2v apparaissent distincts des isolats classiques de HSV-2 et proches de l’alphaherpèsvirus du chimpanzé (ChHV). Afin de caractériser la variabilité de l’ensemble du génome viral, nous avons mis au point une technique d’e��tude utilisant les marqueurs génétiques de type microsatellites, mais des études complémentaires sont nécessaires pour répondre à la question de l’origine du HSV-2v
In this work, the genetic variability of herpes simplex virus type 2 was studied in the context of resistance to antivirals. First, a weak natural polymorphism was reported in HSV-2 concerning the thymidine kinase (TK, UL23 gene) and the DNA polymerase/processivity factor complex (UL30/UL42 genes) with no consequence on the antiviral susceptibility of HSV-2 strains. Then, a novel nonradioactive method for the evaluation the TK phosphorylation activity in vitro was performed to clarify the impact of new mutations previously identified within HSV-2 TK. The aim of these works was to develop a general method for the detection of HSV resistance to antivirals drugs bases solely on genetic analysis. Over a genotypic resistance test, a new genetic variant of HSV-2 was reported with an unexpected high divergence within UL30. The retrospective screening of numerous HSV-2 clinical isolates using a specific real-time PCR assay designed within UL30 gene permitted the identification of additional HSV-2 variants (HSV-2v) leading to an overall prevalence of 2. 2%. All patients were natives from West and Central Africa and were mainly co-infected with HIV. Phylogenetic analysis based on UL30 gene evidenced that HSV-2v isolates clustered in a genetic group distinct from the one of HSV-2 classical isolates close to the chimpanzee alphaherpesvirus ChHV. The molecular study over the whole genome was performed using microsatellite molecular markers. Nevertheless, these results raise the question of the origin of this new virus and further studies are warranted to assess its relationships to other simplexviruses
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20

West, Andrew. "Investigations by mass spectrometry of the interactions of novel serine protease inhibitors with herpes simplex virus type 2 and human cytomegalovirus proteases." Thesis, University of Warwick, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343830.

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21

Winters, Thomas Andrew. "Identification, purification, and characterization of two chromatographically distinct species of uracil-DNA glycosylase from herpes simplex virus type 2 infected human cells /." The Ohio State University, 1990. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487686243821847.

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22

Granados, Carolina. "Botswana’s Adult Identity Mentoring Program (AIM) Public Health Evaluation: The Importance of Counseling and Education to Reduce the Psychosocial Impact on Asymptomatic Youth Diagnosed with Herpes Simplex Virus Type 2." Digital Archive @ GSU, 2012. http://digitalarchive.gsu.edu/iph_theses/240.

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Background: The Division of Global HIV/AIDS at the Centers for Disease Control and Prevention (CDC) is working on a public health evaluation (PHE) in the eastern districts of Botswana. This PHE aims to evaluate the effectiveness of Project AIM, a group-level intervention designed to reduce HIV risk behaviors in youth ages 11 to 14, when combined with the regular Botswana Skills for Life Curriculum, a standard HIV prevention education curriculum in Botswana schools. In order to evaluate Project AIM, a self-report survey and a biological testing for herpes simplex virus type 2 (HSV-2) will be conducted. Methodology: Based on studies done on the psychosocial impact of HSV-2 diagnosis on asymptomatic individuals in the USA, the literature recommends providing pre and post counseling and education to individuals testing for genital herpes to help cope and diminish the psychosocial impact of the diagnosis. In order to prepare Botswana’s clinics and schools participating in the PHE to provide the support for newly diagnosed adolescents with HSV-2, guidance materials were developed for health care practitioners and school guidance teachers. Materials were created using Information Mapping technique to analyze, organize, and present the information, and the Microsoft Office Flesch Kinkade Grade Level (FK) tool to assess the readability levels of the materials. Results: Guidance materials were prepared using the 7±2 theoretical limit of human short-term memory information mapping rule, and the FK grade levels of 6.0 to 8.0 recommended readability scores. Guidance materials included information regarding HSV-2 symptoms, treatment, and prevention. They also included information on the PHE study, youth friendly health services, counseling and education, clinic referrals and contact information. Conclusions: The development of guidance materials for schools and clinic participants of the CDC PHE in Botswana will provide health practitioners and school guidance teachers with accurate HSV-2 information to counsel and educate student participants in this research study. The guidance materials should help students cope with potential psychosocial disorders associated with pre and post diagnosis of HSV-2.
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23

Srivaratharajan, Sangar [Verfasser], Abel [Akademischer Betreuer] Viejo-Borbolla, Paul [Akademischer Betreuer] Becher, and Eike [Akademischer Betreuer] Steinmann. "Identification of the cleavage site of herpes simplex virus type 2 glycoprotein G (gG) and its involvement in gG activities / Sangar Srivaratharajan ; Abel Viejo-Borbolla, Paul Becher, Eike Steinmann." Hannover : Stiftung Tierärztliche Hochschule Hannover, 2019. http://d-nb.info/1202272258/34.

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24

Czechowicz, Julia Stephanie [Verfasser], and Wilhelm [Akademischer Betreuer] Schäfer. "Charakterisierung der Interaktion des Herpes-Simplex-Virus Typ 2 Proteins ICP0 mit der zellulären E3 Ubiquitinligase SIAH-1 und deren Rolle für den viralen Infektionsverlauf / Julia Stephanie Czechowicz ; Betreuer: Wilhelm Schäfer." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2018. http://d-nb.info/1161847391/34.

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25

Whiteley, Alison. "Studies of herpes simplex virus type-1 envelopment." Thesis, University of Cambridge, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.621703.

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26

Wu, Zetang. "Silencing Suppression by Herpes Simplex Virus Type 1." The Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1213287215.

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27

Ewing, Stephen Michael George. "Herpes simplex virus type 1 infection of dendritic leucocytes." Thesis, University of Oxford, 1992. http://ora.ox.ac.uk/objects/uuid:e83750b1-3aa7-452e-a876-be51690252be.

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28

Hodge, Paul Daniel. "The encapsidation of herpes simplex virus type 1 DNA." Thesis, University of Glasgow, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301951.

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Atkinson, Helen Ruth. "Molecular studies of herpes simplex virus type 1 latency." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241568.

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30

Hedner, Ewa. "Herpes Simplex virus type 1 and intraoral wound healing." [Göteborg] : Departments of Clinical Virology, Faculty of Medicine, Oral Microbiology and Oral Surgery, Faculty of Odontology, University of Göteborg, 1993. http://catalog.hathitrust.org/api/volumes/oclc/30761199.html.

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31

Harman, Laura Emily Rose. "Immunological control of herpes simplex virus type 1 latency." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708822.

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Svobodová, Stanislava. "Study of herpes simplex virus type 1 tegument assembly." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607957.

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Naldinho, Souto Raquel Cristina. "Studies of Herpes Simplex Virus type-1 tegument proteins during virus egress." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.613035.

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34

McGeehan, John Edward. "Molecular characterisation of Herpes simplex virus type 1 deoxyuridine triphosphatase." Thesis, University of Glasgow, 1998. http://theses.gla.ac.uk/6104/.

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Analysis of primary sequence data revealed a subset of open reading frames that were predicted to encode HSV-I dUTPases based on five areas of local primary sequence conservation. The differences in the primary sequence organisation of these motif regions allowed the description of two distinct dUTPase classes. The class I dUTPases are encoded by a diverse range of organisms and are characterised by a trimeric arrangement with subunit protein lengths approximating 150 amino acids. The class II dUTPases are specific to the herpesviruses and are characterised by a monomeric arrangement with a protein chain length approximately double that of their class I counterparts. It has been proposed that the class II dUTPases arose by the intragenic duplication of the class I open reading frame. In this thesis the class I structures were used as a basis to investigate the HSV-1 class II dUTPase in terms of structural and evolutionary relationships. To allow a defined approach to functional analysis of the HSV-1 dUTPase a tertiary structural model was generated for the class II enzymes. Following intensive primary sequence analysis a method was devised for comparing class I and class II sequences directly. Secondary structure prediction programs were utilised to judge the basic structural similarities between the two classes allowing the proposition of several defined hypotheses. The available class I structural information was utilised in order to characterise highly conserved structural elements within the class I group. In was then possible to relate this data set to class I primary sequences and subsequently to the generation of a class II model. Various modelling techniques were used based on the constraints on the structural organisation that could achieve a functionally active monomer plus the set of hypotheses defined in the earlier work. Mutagenic analysis of the HSV-1 dUTPase was then possible using the class II model as a reference. Several targets were investigated based on predicated functionally important regions. Analysis of these mutant enzymes was performed using purified recombinant HSV-1 dUTPase expressed from the T7 E.coli expression system.
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Porter, Iain Malcolm. "Characterisation of the herpes simplex virus type 1 mutant, ambUL12." Thesis, University of Glasgow, 2002. http://theses.gla.ac.uk/3959/.

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The herpes simplex virus type 1 (HSV-1) UL12 gene encodes an alkaline nuclease. Although the UL12 gene is not absolutely essential for replication, UL12 null mutants produce 100-1000 fold less viable virus than wt HSV-1. It has been suggested that the alkaline nuclease functions to remove branched structures from high molecular weight concatemeric DNA prior to its cleavage into monomeric genomes that are packaged into viral capsids. Failure to remove the branches results in unstable packaging of DNA into capsids which fail to egress from the nucleus. This thesis describes detailed characterisation of the HSV-1 mutant, ambUL12 (Patel et al., 1996) which fails to express the alkaline nuclease due to the insertion of an amber stop codon into the UL12 open reading frame. The ability of ambUL12 to replicate and package both viral genomic DNA and amplicons (plasmids containing the HSV-1 origin of replication and DNA encapsidation signal) was examined. In contrast to results obtained with other alkaline nuclease mutants, which replicate and package DNA with close to wt HSV-1 efficiency (Shao et al., 1993; Martinez et al., 1996b), ambUL12 displayed a 3-5 fold drop in replication and a 15-20 fold drop in packaging of genomic DNA. Similar reductions were observed in the replication and packaging of amplicon DNA. The replication and packaging of amplicons by ambUL12 in these transient assays could be partially complemented when UL12 was supplied in trans. Close inspection of the DNA molecules synthesised during transient assays demonstrated that amplicon replication intermediates are complex high molecular weight concatemers that undergo intermolecular recombination, analogous to viral DNA replication intermediates.
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Preetha, Balan K. V. "Analysis of dispensable glycoproteins of herpes simplex virus type 1." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.320012.

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Galdiero, Massimiliano. "Mutagenesis of glycoprotein H of herpes simplex virus type 1." Thesis, University of Cambridge, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.624784.

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38

Sayers, Charlotte. "Herpes simplex virus type 1 infection of human keratinocyte cells." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/11112.

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Infection of herpes simplex virus type 1 (HSV-1) begins at the epidermis, a stratified layer composed primarily of keratinocytes. The physiologically relevant cell type for the study of HSV-1 assembly is therefore the human keratinocyte. Nonetheless, relatively little is known about the replication of HSV-1 in this natural host cell. Comparison of virus growth in monolayers of keratinocyte cells and Vero cells, a routinely used cell line for HSV-1 studies, revealed that these keratinocytes support a more productive virus replication than Vero cells. Furthermore, newly assembled virus is produced more rapidly in keratinocytes and this enhancement occurs prior to, or upon the initiation of immediate early gene transcription. This augmented replication in keratinocytes can be at least partially attributed to the method of entry of the virus. We have found by penetration assays and electron microscopy that the virus is able to penetrate keratinocyte cells much more rapidly than Vero cells. We have also shown that the virus entry mechanism is more efficient at lower temperatures in nTERT cells, with virus entering cells at temperatures as low as 7°C. Additionally preliminary work implies that depletion of one of the herpes virus entry receptors, Nectin-1, does not affect entry into nTERT cells, whereas entry is reduced up to 65% in HeLa cells. Taken together, these results imply a role for other entry receptors, possibly as yet unidentified, in the entry of human keratinocyte cells. This work also identifies a role for cellular Rab proteins, GTPases essential for the regulation of vesicle trafficking, in HSV-1 infection of keratinocytes. In particular Rab6, which was also found to play a role in infected HeLa cells (Elliott Group), appears to have a similar function in both these cells and together support a model for HSV-1 morphogenesis involving Rab-regulated vesicle trafficking of viral glycoproteins to the cell surface. Several other Rabs identified by this screen now provide interesting opportunities to elucidate further roles of Rab proteins in HSV-1 infection of keratinocyte cells. This project has broadly characterised the replication of HSV-1 in keratinocyte cells and explored the role of Rab GTPases in virus trafficking within keratinocytes - a cell type that is physiologically relevant to infection.
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39

Ebert, Steven Neill. "Interactions between host type II topoisomerases and herpes simplex virus type I /." The Ohio State University, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487688507502228.

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40

Kew, Chun, and 喬駿. "Inhibition of PACT mediated type 1 interferon production by herpes simplex virus type 1 Us11 protein." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206481.

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Mammals have complicated antiviral innate immunity to combat viral infection and this poses a strong selection pressure on the viruses. As a result, many viruses have evolved different strategies to disrupt the function of hosts’ antiviral innate immunity. Herpes simplex virus type 1 (HSV-1) is one of the examples. HSV-1 is a common and important human pathogen. HSV-1 infection induces type I interferons (IFNs) which restrict viral replication potently. To ensure persistent infection and successful replication, HSV-1 encodes several IFN-suppressing proteins. One example is Us11. Interaction between Us11 and various cellular proteins, such as PKR, RIG-I and PACT, were shown by other studies. However, exactly how Us11 suppresses IFN function remains to be elucidated. In this study, I discovered that Us11 specifically inhibits PACT induced activation of RIG-I. In HSV-1 infected cells, PACT and Us11 associate with each other tightly and this interaction prevents the interaction of PACT with RIG-I. It was also found that RNA binding domains on both PACT and Us11 are important for the association. In infection experiments, the increased production of IFN- during the infection of PACT-competent cells with Us11-deficient HSV-1 recombinant virus was not observed in infected PACT-compromised cells, suggesting the requirement of PACT for Us11 suppression of IFN production. To conclude, this study provides an explanation for Us11 antagonism of IFN production. My findings suggest that PACT is a novel target of HSV-1 IFN-antagonizing protein Us11.
published_or_final_version
Biochemistry
Master
Master of Philosophy
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41

Wang, Yisheng. "Characterizations of DNA replication proteins from herpes simplex virus type 1." Diss., The University of Arizona, 1990. http://hdl.handle.net/10150/185295.

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This study was designed to characterize two DNA replication proteins from herpes simplex virus type 1 (HSV-1): the major DNA binding protein (ICP8) and the DNA polymerase. The two proteins are among the seven proteins required for viral DNA synthesis. Four areas were investigated. First, the ICP8 protein was purified from an overproducing cell and showed to behave the same as the viral protein in interacting with DNA. To define the DNA-binding domain of the protein, a proteolytic fragment with the same DNA-binding specificity as the intact protein was identified by a protein blotting assay. N-terminal protein sequencing located the fragment between residues 300 and about 849 in the intact protein. This fragment contains some features important for DNA binding. Second, the DNA polymerase was found to replicate non-processively in vitro. The ICP8 protein slightly stimulated the polymerase activity at lower concentrations and inhibited its activity as the ICP8 concentration increased. Third, to define the functional domain of the DNA polymerase, a fragment of the polymerase predicted to contain both the polymerase and 3$\sp\prime$-5$\sp\prime$ exonuclease activities was overexpressed in Escherichia coli. The fragment was partially purified and its enzymatic activity was examined. Finally, to identify polymerase residues involved in substrate binding, three amino acid changes in polymerase mutants with altered drug sensitivities have been identified by DNA sequencing. Two mutations, affecting nucleotide binding, occur near two highly conserved regions which constitute part of a putative nucleotide binding site. This result indicates that two more residues are important for substrate binding. The third mutation, affecting pyrophosphate binding, occurs upstream of any previously known mutations. This result may indicate a new region involved in substrate binding.
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42

Grey, F. E. "Investigation of factors involved in herpes simplex virus type 1 pathogenesis." Thesis, University of Cambridge, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599699.

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The mouse model has been extensively used in studies of HSV pathogenesis and has led to a greater understanding of many aspects of the virus life cycle and viral replication in vivo. The current study makes use of the mouse model to investigate two aspects of viral pathogenesis. The initial project concerns viral resistance to the antiviral drug Aciclovir (ACV) and the pathogenesis of a resistant clinical isolate. The aim of the second project was to investigate the effects of disrupting antigen presentation by MHC class I on the replication and pathogenesis of HSV-1. Aciclovir is a highly effective drug in the treatment of herpetic infections. Its effectiveness, however, is undermined by the emergence of resistance virus isolates that can cause serious disease in immunocompromised patients. In the majority of cases resistance occurs through a mutation that disrupts the TK gene of HSV and is normally associated with attenuation of neurovirulence. In this study a clinical isolate resistant to ACV (4B) was found to display a high level of neurovirulence despite a double G insertion mutation that would theoretically disrupt all TK activity. Following inoculation of the mice the virus was able to replicate efficiently in dorsal root ganglia during acute infection and was able to reactivate from latency. Furthermore, plaque purified isolates of 4B uniformly expressed a very low level of TK activity. Disruption of the TK gene of 4B led to a loss of the low level of TK activity and a loss in the ability to replicate in the ganglia of mice and to reactivate from latency. Further investigation showed that the ability of isolate 4B to replicate in the nervous system of mice was due to the virus gaining an additional G residue, rescuing the original frameshift mutation and allowing the virus to express wild type levels of TK. The neurovirulence associated with 4B is therefore due to phenotypic reversion. The immune response of the host plays an important role in shaping the pathogenesis of HSV. To counteract the antiviral effects of the immune system HSV encodes a number of genes involved in immune evasion.
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43

Adamson, Walt Eric. "Mapping the proteins of the herpes simplex virus type 1 capsid." Thesis, University of Glasgow, 2006. http://theses.gla.ac.uk/3963/.

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The aims of the work presented in this thesis were to use a variety of mutagenesis techniques to investigate the proteins of the HSV-1 capsid. Triplexes are heterotrimers formed by two proteins in a 1:2 stoichiometry. The single-copy protein is called VP19C, and the dimeric protein is VP23. Insertional and deletional mutagenesis was carried out on VP19C and the effects of the mutations on virus growth and capsid assembly were examined. Insertional mutagenesis showed that VP19C can be divided into three regions with respect to their ability to tolerate five amino acid insertions, with two regions of approximately 100 amino acids at the N- and C-terminal regions of the protein being more tolerant of such insertions than a ~350 amino acid central region. The N-terminal ~100 amino acids of the protein, which are particularly insensitive to insertional mutagenesis, correspond to a region that is poorly conserved among herpesviruses. Some, but not all, severely disabled mutants were compromised in their ability to bind VP23 and VP5. Analysis of deletional mutants revealed the presence of an unusual nuclear localisation signal (NLS) near the N-terminus of VP19C. This was mapped to a 33 amino acid region by fusion of specific sequences to a green fluorescent protein (GFP) marker. By replacing the endogenous NLS with that from the simian virus 40 (SV40) large T antigen, we were able to show that the first 45 amino acids of VP19C were not essential for assembly of functional capsids and infectious virus particles. However, removing the first 63 amino acids resulted in the formation of aberrant capsids and prevented virus growth, suggesting that the poorly-conserved N-terminal sequences have some as-yet-unidentified function.
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44

Desai, Prashant Jayant. "Studies on glycoprotein n H of herpes simplex virus type 1." Thesis, University of Cambridge, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.238658.

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45

Gompels, V. A. "Identification and analyses of a herpes simplex virus type 1 glycoprotein." Thesis, University of Cambridge, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.373674.

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46

Ueno, Shohta. "Functional analysis of the herpes simplex virus type-1 glycoprotein H." Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608640.

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47

Ren, Yudan. "Glycoprotein M and ESCRT in herpes simplex virus type 1 assembly." Thesis, University of Cambridge, 2012. https://www.repository.cam.ac.uk/handle/1810/241516.

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Herpes simplex virus type 1 (HSV-1) has a large linear double-stranded DNA genome in an icosahedral capsid shell, a cell-derived lipid envelope and a proteinaceous tegument layer. There are over fifty viral proteins and many host proteins identified in HSV-1 virions. The final formation of mature virus particles requires the membrane wrapping of tegumented capsids in the cytoplasm, a process termed secondary envelopment. This process involves the coordination of numerous viral and cellular proteins and results in double-membrane structures with enveloped virions contained within cellular vesicles. Mature viruses are then released through the fusion of these virion-containing vesicles and plasma membranes. This thesis describes investigation into the functions of viral glycoprotein M (gM) and the cellular Endosomal Sorting Complexes Required for Transport (ESCRT) in secondary envelopment. Firstly, it has been reported that gH/L can be efficiently internalised and targeted to the TGN by the co-expression of gM in transfection assays. In order to examine the role of gM in guiding the localisation of viral proteins in infected cells, a HSV-1 gM deletion virus (∆gM), and its revertant virus were constructed. The major phenotype demonstrated was that the absence of gM caused the internalisation of cell surface gH/L to be inhibited and higher levels of gH/L to be observed on the cell surface. Further, lower levels of gH/L were detected in purified ∆gM virions, which was in agreement with the delayed entry kinetics, smaller plaque sizes and greater replication deficits at low multiplicity of infection observed in ∆gM infected cells. Over all the results presented in this thesis demonstrate that in infected cells the efficient incorporation of gH/L into virions relies on the function of gM in HSV-1. Secondly, during HSV-1 secondary envelopment the budding and scission of the viral envelope from the host membrane share topological similarities with the formation of intraluminal vesicle in multivesicular bodies, retrovirus budding, and abscission at the end of cytokinesis, processes that require the cellular ESCRT machinery. There are four multiprotein ESCRT complexes and many associated proteins involved in their regulation. It has been previously shown that the ESCRT-III complex and a functional ATPase VPS4 are required for HSV-1 secondary envelopment, but different from the strategy utilised by HIV-1, the recruitment of ESCRT during HSV-1 infection is independent of TSG101 and/or ALIX. Data presented in this thesis demonstrate that CHMP4A/B/C proteins of the ESCRT-III complex are specifically crucial for HSV-1 secondary envelopment. Simultaneous depletion of CHMP4A/B/C proteins significantly inhibited HSV-1 replication. Ultrastructure analysis revealed that there were virtually no extracellular virions in CHMP4A/B/C depleted samples while more free capsids were observed in the cytoplasm, although the nuclear capsids and primary envelopment events appeared to be normal. In order to identify interactions between HSV-1 and ESCRT proteins, 22 HSV-1 tegument proteins were cloned and tested against a panel of ESCRT and ESCRT-associated proteins in yeast two-hydrid assays. Analysis of positive hits from yeast two-hybrid interaction screens using GST pull-down, co-immunoprecipitation and protein co-localisation assays have validated interactions of pUL47 with CC2D1A/1B, CIN85, CHMP6 and ALIX, pUL46 and pUL49 with CC2D1A/1B and CIN85, and pUL16 with CC2D1A/1B. Furthermore, the newly identified ESCRT associated proteins CC2D1A and CC2D1B have been detected in purified virions. The role of the identified ESCRT proteins in HSV-1 replication has been investigated using siRNA depletion. Unfortunately siRNA depletions of the various ESCRT candidates individually or in combinations did not show any significant effect on HSV-1 replication. Overall these data suggest that unlike HIV and other retroviruses, HSV-1 has evolved multiple parallel pathways to hijack the ESCRT machinery to facilitate its replication, particularly, through the interactions that lead directly to the recruitment of CHMP4A/B/C proteins. Disruption of some of these pathways did not prevent HSV-1 replication in tissue culture, suggesting any one potential pathway is sufficient for ESCRT recruitment to sites of HSV-1 assembly.
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48

Mouzakitis, Gerasimos. "Characterization of the herpes simplex virus type 1 tegument protein VP22." Thesis, Imperial College London, 1998. http://hdl.handle.net/10044/1/11842.

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49

Zhou, Amy Yuan. "Exploring the functional role of herpes simplex virus type-1 glycoprotein H in virus entry." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648658.

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50

Sullivan, Veronica. "Analysis of the herpes simplex virus type 1 glycoproteins using recombinant vaccinia virus vectors." Thesis, University of Cambridge, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292957.

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