Academic literature on the topic 'Flavivirus diagnosis'
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Journal articles on the topic "Flavivirus diagnosis"
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Wee, Sheena, Asfa Alli-Shaik, Relus Kek, Hannah L. F. Swa, Wei-Ping Tien, Vanessa W. Lim, Yee-Sin Leo, Lee-Ching Ng, Hapuarachchige C. Hapuarachchi, and Jayantha Gunaratne. "Multiplex targeted mass spectrometry assay for one-shot flavivirus diagnosis." Proceedings of the National Academy of Sciences 116, no. 14 (March 18, 2019): 6754–59. http://dx.doi.org/10.1073/pnas.1817867116.
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Targeted proteomic mass spectrometry is emerging as a salient clinical diagnostic tool to track protein biomarkers. However, its strong analytical properties have not been exploited in the diagnosis and typing of flaviviruses. Here, we report the development of a sensitive and specific single-shot robust assay for flavivirus typing and diagnosis using targeted mass spectrometry technology. Our flavivirus parallel reaction monitoring assay (fvPRM) has the ability to track secreted flaviviral nonstructural protein 1 (NS1) over a broad diagnostic and typing window with high sensitivity, specificity, extendibility, and multiplexing capability. These features, pivotal and pertinent to efficient response toward flavivirus outbreaks, including newly emerging flavivirus strains, circumvent the limitations of current diagnostic assays.fvPRM thus carries high potential in positioning itself as a forerunner in delivering early and accurate diagnosis for disease management.
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Musso, Didier, and Philippe Desprès. "Serological Diagnosis of Flavivirus-Associated Human Infections." Diagnostics 10, no. 5 (May 14, 2020): 302. http://dx.doi.org/10.3390/diagnostics10050302.
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Arthropod-borne viruses (arboviruses) belonging to the Flavivirus genus of the Flaviviridae family, are a major public health threat in tropical and subtropical regions, and have recently become a medical concern in temperate zones. Most flaviviruses are classified as zoonotic viruses. Human flavivirus infections can be asymptomatic, responsible for unspecific symptoms in the first few days following infection, or responsible for severe complications potentially resulting in death. During the first days following symptom onset, laboratory diagnosis of acute human flavivirus infection is mainly based on molecular detection of the viral genome by RT-PCR methods, followed by the capture of specific antibodies using serological tests after the first week of infection. The detection of antibodies that have virus neutralizing activity can be used to confirm flavivirus infection. However, human flavivirus infections induce the production of cross-reactive antibodies, often making serology inconclusive. Indeed, serological diagnosis of flavivirus infection can be hampered by a patient’s history of flavivirus exposure, particularly in regions where multiple antigenically related flaviviruses co-circulate. We focus our mini review on conventional immunoassays that allow the diagnosis of major flavivirus-associated human infections in basic, routine and high-profile central health centers; and the interpretation of diagnostic serology tests for patients living within different epidemiological situations.
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Thibodeaux, Brett A., and John T. Roehrig. "Development of a Human-Murine Chimeric Immunoglobulin M Antibody for Use in the Serological Detection of Human Flavivirus Antibodies." Clinical and Vaccine Immunology 16, no. 5 (March 18, 2009): 679–85. http://dx.doi.org/10.1128/cvi.00354-08.
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ABSTRACT Current diagnosis of human flaviviral infections relies heavily on serological techniques such as the immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay (MAC-ELISA). Broad application of this assay is hindered by a lack of standardized human positive-control sera that react with the wide variety of flaviviruses that can cause human disease, e.g., dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), Japanese encephalitis virus (JEV), and St. Louis encephalitis virus (SLEV). We have created a human-murine chimeric antibody combining the variable regions of the broadly flavivirus cross-reactive murine monoclonal antibody (MAb) 6B6C-1 and the constant region of human IgM to produce a standardized reagent capable of replacing human positive-control sera in a MAC-ELISA for the diagnosis of all human flaviviral infections. The human-murine chimeric IgM antibody secreted from plasmid-transformed Sp2/0-Ag14 cells had a level of serological activity identical to that of 6B6C-1 as measured by ELISA, immunoblotting, and MAC-ELISA for multiple members of the flavivirus genus, including WNV, SLEV, YFV, DENV, and JEV.
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Beck, Cécile, Philippe Desprès, Sylvie Paulous, Jessica Vanhomwegen, Steeve Lowenski, Norbert Nowotny, Benoit Durand, et al. "A High-Performance Multiplex Immunoassay for Serodiagnosis of Flavivirus-Associated Neurological Diseases in Horses." BioMed Research International 2015 (2015): 1–13. http://dx.doi.org/10.1155/2015/678084.
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West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV) are flaviviruses responsible for severe neuroinvasive infections in humans and horses. The confirmation of flavivirus infections is mostly based on rapid serological tests such as enzyme-linked immunosorbent assays (ELISAs). These tests suffer from poor specificity, mainly due to antigenic cross-reactivity among flavivirus members. Robust diagnosis therefore needs to be validated through virus neutralisation tests (VNTs) which are time-consuming and require BSL3 facilities. The flavivirus envelope (E) glycoprotein ectodomain is composed of three domains (D) named DI, DII, and DIII, with EDIII containing virus-specific epitopes. In order to improve the serological differentiation of flavivirus infections, the recombinant soluble ectodomain of WNV E (WNV.sE) and EDIIIs (rEDIIIs) of WNV, JEV, and TBEV were synthesised using theDrosophilaS2 expression system. Purified antigens were covalently bonded to fluorescent beads. The microspheres coupled to WNV.sE or rEDIIIs were assayed with about 300 equine immune sera from natural and experimental flavivirus infections and 172 nonimmune equine sera as negative controls. rEDIII-coupled microspheres captured specific antibodies against WNV, TBEV, or JEV in positive horse sera. This innovative multiplex immunoassay is a powerful alternative to ELISAs and VNTs for veterinary diagnosis of flavivirus-related diseases.
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Chiou, Shyan-Song, Wayne D. Crill, Li-Kuang Chen, and Gwong-Jen J. Chang. "Enzyme-Linked Immunosorbent Assays Using Novel Japanese Encephalitis Virus Antigen Improve the Accuracy of Clinical Diagnosis of Flavivirus Infections." Clinical and Vaccine Immunology 15, no. 5 (March 12, 2008): 825–35. http://dx.doi.org/10.1128/cvi.00004-08.
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ABSTRACT The cross-reactive antibodies induced by flavivirus infections confound serodiagnosis and pathogenesis, especially in secondary infections caused by antigenically closely related yet distinct flaviviruses. The envelope (E) glycoprotein fusion peptide contains immunodominant cross-reactive determinants. Using a recombinant Japanese encephalitis virus (JEV) premembrane and E expression plasmid producing JEV virus-like particles (VLPs), dramatic reductions in cross-reactivity were produced by the G106K-L107D (KD) double-mutant VLP against a panel of flavivirus murine monoclonal antibodies. Human serum panels from patients with recent flavivirus infections were analyzed to compare the accuracy of JEV wild-type (WT) and KD VLPs as serodiagnostic antigens in enzyme-linked immunosorbent assays. Statistical analysis demonstrated significant differences in assay performances for accurate determination of current JEV infections between WT and KD antigens by detecting immunoglobulin M antibodies at a serum dilution of 1:4,000 (likelihood ratios = 2.74 [WT] and 22 [KD]). The application and continued development of cross-reactivity-reduced antigens should improve both flavivirus infection serodiagnosis and estimates of disease burden.
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Thibodeaux, Brett A., Amanda N. Panella, and John T. Roehrig. "Development of Human-Murine Chimeric Immunoglobulin G for Use in the Serological Detection of Human Flavivirus and Alphavirus Antibodies." Clinical and Vaccine Immunology 17, no. 10 (August 25, 2010): 1617–23. http://dx.doi.org/10.1128/cvi.00097-10.
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ABSTRACT Diagnosis of human arboviral infections relies heavily on serological techniques such as the immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) and the indirect IgG ELISA. Broad application of these assays is hindered by the lack of standardized positive human control sera that react with a wide variety of flaviviruses (e.g., dengue, West Nile, yellow fever, Japanese encephalitis, Saint Louis encephalitis, and Powassan viruses), or alphaviruses (e.g., Eastern equine encephalitis, Western equine encephalitis, Venezuelan equine encephalitis, and chikungunya viruses) that can cause human disease. We have created human-murine chimeric monoclonal antibodies (cMAbs) by combining the variable regions of flavivirus (6B6C-1) or alphavirus (1A4B-6) broadly cross-reactive murine MAbs (mMAbs) with the constant region of human IgG1. These cMAbs may be used as standardized reagents capable of replacing human infection-immune-positive control sera in indirect IgG ELISA for diagnosis of all human flaviviral or alphaviral infections. The IgG cMAbs secreted from plasmid-transformed Sp2/0-Ag14 cells had serological activity identical to that of the parent mMAbs, as measured by ELISA using multiple flaviviruses or alphaviruses.
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Khristunova, Ekaterina, Elena Dorozhko, Elena Korotkova, Bohumil Kratochvil, Vlastimil Vyskocil, and Jiri Barek. "Label-Free Electrochemical Biosensors for the Determination of Flaviviruses: Dengue, Zika, and Japanese Encephalitis." Sensors 20, no. 16 (August 16, 2020): 4600. http://dx.doi.org/10.3390/s20164600.
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A highly effective way to improve prognosis of viral infectious diseases and to determine the outcome of infection is early, fast, simple, and efficient diagnosis of viral pathogens in biological fluids. Among a wide range of viral pathogens, Flaviviruses attract a special attention. Flavivirus genus includes more than 70 viruses, the most familiar being dengue virus (DENV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV). Haemorrhagic and encephalitis diseases are the most common severe consequences of flaviviral infection. Currently, increasing attention is being paid to the development of electrochemical immunological methods for the determination of Flaviviruses. This review critically compares and evaluates recent research progress in electrochemical biosensing of DENV, ZIKV, and JEV without labelling. Specific attention is paid to comparison of detection strategies, electrode materials, and analytical characteristics. The potential of so far developed biosensors is discussed together with an outlook for further development in this field.
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Taylor, Carmel, Russell Simmons, and Ina Smith. "Development of Immunoglobulin M Capture Enzyme-Linked Immunosorbent Assay To Differentiate Human Flavivirus Infections Occurring in Australia." Clinical Diagnostic Laboratory Immunology 12, no. 3 (March 2005): 371–74. http://dx.doi.org/10.1128/cdli.12.3.371-374.2005.
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ABSTRACT We report the development of a flavivirus immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (MAC-ELISA) which improves the determination of an infecting flavivirus serotype over that by current serological methods. A panel of 165 IgM-positive sera from flavivirus patients with specific diagnostic results was tested by the flavivirus MAC-ELISA using a panel of 10 antigens. For 134 of these sera (81.2%), the highest reactivity was demonstrated against the infecting virus, which was consistent with the original diagnostic result. Specific antibody reactions inconsistent with the original diagnosis were found for six sera (3.6%). In our experience, the flavivirus-serotyping ELISA provides a rapid and accurate alternative to other serological tests, such as hemagglutination inhibition, for the specific diagnosis of flavivirus infections.
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Chu, Charleen T., David N. Howell, Joel C. Morgenlander, Christine M. Hulette, Roger E. McLendon, and Sara E. Miller. "Electron Microscopic Diagnosis of Human Flavivirus Encephalitis." American Journal of Surgical Pathology 23, no. 10 (October 1999): 1217. http://dx.doi.org/10.1097/00000478-199910000-00006.
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Landry, Marie Louise, and Kirsten St. George. "Laboratory Diagnosis of Zika Virus Infection." Archives of Pathology & Laboratory Medicine 141, no. 1 (October 20, 2016): 60–67. http://dx.doi.org/10.5858/arpa.2016-0406-sa.
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Context.—The rapid and accurate diagnosis of Zika virus infection is an international priority. Objective.—To review current recommendations, methods, limitations, and priorities for Zika virus testing. Data Sources.—Sources include published literature, public health recommendations, laboratory procedures, and testing experience. Conclusions.—Until recently, the laboratory diagnosis of Zika infection was confined to public health or research laboratories that prepared their own reagents, and test capacity has been limited. Furthermore, Zika cross-reacts serologically with other flaviviruses, such as dengue, West Nile, and yellow fever. Current or past infection, or even vaccination with another flavivirus, will often cause false-positive or uninterpretable Zika serology results. Detection of viral RNA during acute infection using nucleic acid amplification tests provides more specific results, and a number of commercial nucleic acid amplification tests have received emergency use authorization. In addition to serum, testing of whole blood and urine is recommended because of the higher vial loads and longer duration of shedding. However, nucleic acid amplification testing has limited utility because many patients are asymptomatic or present for testing after the brief period of Zika shedding has passed. Thus, the greatest need and most difficult challenge is development of accurate antibody tests for the diagnosis of recent Zika infection. Research is urgently needed to identify Zika virus epitopes that do not cross-react with other flavivirus antigens. New information is emerging at a rapid pace and, with ongoing public-private and international collaborations and government support, it is hoped that rapid progress will be made in developing robust and widely applicable diagnostic tools.
Dissertations / Theses on the topic "Flavivirus diagnosis"
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Denis, Jessica. "Discrimination sérologique de flavivirus, étude du domaine III de la protéine d’enveloppe du virus Zika comme cible d’anticorps spécifiques. High specificity and sensitivity of Zika EDIII-based ELISA diagnosis highlighted by a large human reference panel. Vector-Borne Transmission of the Zika Virus Asian Genotype in Europe." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASS078.
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Le virus Zika fait partie du genre des Flavivirus comme le virus de la dengue. Ils sont transmis par les moustiques du genre Aedes. En 2015, une épidémie a causé plus de 700 000 infections, à l’origine de microcéphalies chez les fœtus et de syndromes de Guillain Barré. Pour la première fois, la transmission d’un arbovirus par voie sexuelle est mise en évidence. Les Flavivirus co-circulent dans de nombreux pays, parfois de façon concomitante. Leurs infections induisent des anticorps capables de reconnaitre différents Flavivirus. Cette réactivité croisée peut conduire, en fonction de leur concentration et de leur affinité à une séro-neutralisation virale croisée ou au contraire aggraver la pathologie liée à une seconde infection. Deux problématiques dues à cette réaction croisée apparaissent, (i) il est difficile de rendre un sérodiagnostic fiable et (ii) un vaccin pourrait induire, au contraire d’une protection, une aggravation des pathologies. Au cours de ces travaux, nous avons évalué la fiabilité de reconnaissance du domaine III de la protéine d’enveloppe du virus Zika par les anticorps qu’une infection virale induit chez l’homme. Ce domaine porte des épitopes reconnus spécifiquement par des IgG produits lors d’une infection par ce virus ce qui en fait un marqueur spécifique. L’ELISA mis au point a une sensibilité de 92% et une spécificité de 90%. Avec cet outil nous avons diagnostiqué un cas ancien présent dans une zone pré-épidémique ainsi qu’un cas autochtone dans le sud de la France en 2019. Le suivi de la cinétique d’apparition et de disparition des IgM et des IgG de patients pendant une année nous a permis d’estimer une fenêtre d’utilisation de notre diagnostic, tout en caractérisant les réponses immunitaires humorales liées à l’intensité des infections, la gravité de la pathologie ainsi que la présence d’une cicatrice sérologique. Enfin, l’étude d’anticorps induits par ce domaine complexé à une nanoparticule dans un modèle animal a montré un fort pouvoir adjuvant de ces nanoparticules ainsi qu’une reconnaissance spécifique du virus ZikaThe Zika virus, like the dengue virus, is a Flavivirus and both are transmitted by Aedes mosquitoes. In 2015, an epidemic caused more than 700,000 infections, leading to foetal microcephaly and Guillain Barré syndrome. In addition, sexual transmission of the Zika virus was demonstrated for the first time. Flaviviruses co-circulate in many countries, sometimes concomitantly. Infections with Flaviviruses induce cross-reacting antibodies, leading to cross-neutralization or, on the contrary, worsening of the disease following a second infection, depending on their concentration and affinity. Such cross-reaction leads to two principle problems: (i) it is difficult to make a reliable serodiagnosis and (ii) a vaccine may aggravate the disease instead of providing protection. Here, we evaluated the reliability of antibodies induced during human infections to recognise envelope protein domain III of the Zika virus. This domain carries epitopes recognized by the IgG produced during a Zika virus infection, making it a specific marker. An ELISA developed to detect this domain shows 92% sensitivity and 90% specificity. We used this tool to diagnose an old case from a pre-epidemic area as well as an indigenous case from the south of France in 2019. Monitoring the kinetics of the appearance and disappearance of IgM and IgG in the blood of patients for one year allowed us to estimate the window of use for our diagnostic tool, while characterizing the humoral immune responses linked to the epidemic and the severity of the disease, as well as the presence of a serological scar. Finally, the study of antibodies induced by this domain complexed to nanoparticles in an animal model showed such nanoparticles to be a strong adjuvant and the antibodies to specifically recognize the Zika virus
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Beck, Cécile. "Nouvelles stratégies diagnostiques et thérapeutiques contre les flavivirus neurotropes en médecine vétérinaire." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS083/document.
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Les flavivirus ayant un impact en médecine vétérinaire sont largement distribués dans le monde (à l’exemple de la fièvre West Nile (WNF) présente sur les cinq continents ou de l’Encéphalite japonaise (EJ) en Asie du Sud-Est) et sont responsables de maladies à dominante neurologique chez l’homme et/ou le cheval.La virémie étant généralement brève lors de ces infections virales, les méthodes de diagnostic utilisées sont essentiellement sérologiques. Or le chevauchement fréquent des aires de répartition des flavivirus complique le diagnostic sérologique. En effet, des réactions sérologiques croisées entre flavivirus sont observées lors de l’utilisation de méthodes de diagnostic usuelles telles que l’ELISA et l’immunofluorescence (IF). Les résultats sérologiques doivent donc être confirmés par la méthode fastidieuse de séroneutralisation (SNT) virale avec les différents flavivirus existants dans la région. De plus, le risque d’émergence sur un territoire donné de nouveaux flavivirus comme le virus Zika au Brésil ou en Amérique du Nord ne peut être exclu.Nous avons donc développé dans la première partie de ce travail une nouvelle stratégie de diagnostic sérologique multiplexe à l’aide de la méthode d’immuno-essai (MIA) sur billes. Sachant que la glycoprotéine d’enveloppe soluble (sE) des flavivirus est divisée en 3 domaines (D) structuraux, DI, DII et DIII et que les épitopes du DIII sont spécifiques de chaque flavivirus, des protéines EDIII recombinantes de différents flavivirus d’intérêt ont été synthétisées en système d’expression Drosophila S2 et leur antigénicité a été testée sur sérums équins et ovins. Nous avons obtenu des résultats très encourageants en démontrant que l’utilisation des EDIII associée avec la capacité de multiplexage de la méthode MIA apparaît comme une réponse adaptée au défi du diagnostic sérologique des infections à flavivirus.Nous avons en outre utilisé la même méthode de multiplexage mais avec des antigènes NS1 du WNV pour mettre en place un test DIVA (Differentiating Infected from Vaccinated Animals) permettant de différencier les chevaux infectés par le WNV des chevaux vaccinés avec un vaccin recombinant WNV.Un autre écueil en médecine vétérinaire est le traitement des affections à flavivirus. En effet l’arsenal thérapeutique est limité et le traitement est avant tout symptomatique. Nous avons dans la seconde partie de ce travail testé in vitro une molécule antivirale à large spectre, le sr1057 sur nos virus d’intérêt (WNV et JEV). Cette molécule qui provient d’une stratégie de criblage développée par l’Institut Pasteur a probablement pour cible la cellule de l’hôte car elle est capable d’inhiber des virus très différents, à génome à ARN de polarité positive ou négative et ADN.Les résultats que nous avons obtenus avec ce composé sont en demi-teinte pour les flavivirus testés avec une efficacité démontrée pour le JEV mais plus modeste pour le WNV. Ils n’excluent cependant pas une possible utilisation de cet antiviral en médecine vétérinaire équine car une activité inhibitrice in vitro sur les virus de l’Herpes équin de type I et de l’artérite virale a été confirmée par d’autres collaborateursFlaviviruses with a major impact in veterinary medicine are widely distributed (e.g. West Nile fever (WNF) has spread across the five continents and Japanese Encephalitis (JE) is reported in South-East Asia) and are mainly responsible for neurological diseases in humans and/or horses.After flavivirus infection, viremia in mammal hosts is generally short and consequently indirect methods are mostly used to diagnose flavivirus infections. However, frequent spatial overlapping in their circulation areas renders the interpretation of serological assays difficult. Indeed, cross-reactions between flaviviruses are observed in rapid serological tests such as in ELISA and immunofluorescence assays (IFA). Serological assay results should thus be confirmed by the tedious comparative virus neutralization test (VNT) using a panel of viruses known to circulate in the area. Moreover, the risk of emergence of new flaviviruses such as reported recently with the Zika virus in Brazil or in North America should be considered when studying flavivirus epidemiology.In the first section, a new strategy aiming at improving the serological diagnosis of flavivirus infections was developed using the multiplexing capacity of microsphere immunoassays (MIA). The flavivirus soluble envelope (sE) glycoprotein ectodomain is composed of three domains (D), e.g. DI, DII and DIII, with EDIII containing virus-specific epitopes. Recombinant EDIIIs of different flaviviruses were synthesized in the Drosophila S2 expression system. The microspheres coupled with rEDIIIs were assayed with equine and ovine sera from natural and experimental flavivirus infections or non-immune samples. Very encouraging results have been obtained and this innovative multiplex immunoassay based on flavivirus rEDIIIs appears to be a powerful alternative to ELISAs and VNTs for veterinary diagnosis of flavivirus-related diseases.MIA with WNV nonstructural 1 protein were also implemented to differentiate Infected from Vaccinated Animals (DIVA). Such a DIVA approach was only successful when horses had been immunized with a recombinant canarypox vaccine, while horses receiving inactivated WNV vaccine developed immune responses close to the ones induced after natural infection.Another pitfall in veterinary medicine is the lack of therapeutics for viral diseases and specifically for flaviviruses. The therapeutic arsenal is indeed rather limited and animals are generally administered supportive treatments only. In the second part, the results of the in vitro testing of a broad spectrum antiviral named sr1057 on WNV and JEV replication are presented. This chemical, identified from a unique screening strategy developed by Pasteur Institute, is probably targeting the host cell and was found to inhibit the replication of varied RNA and DNA viruses belonging to different virus families. The sr1057 compound was not as efficient at inhibiting the replication of flaviviruses as for other RNA+ viruses, with a modest antiviral effect demonstrated for WNV and a higher efficacy on JEV. This antiviral presents however potentials for applications in equine veterinary medicine because it efficiently inhibited equine herpes virus-1 and equine arteritis virus in vitro, as clearly shown by other collaborators
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Brient-Litzler, Elodie. "Biocapteurs fluorescents autonomes dérivés d'ankryines artificielles et bioconjugués pour le diagnostic précoce d'infections flavivirales." Paris 6, 2009. http://www.theses.fr/2009PA066014.
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Les biocapteurs fluorescents autonomes (FA) sont des molécules fixatrices d’antigènes couplées à un fluorophore, dont l’intensité de fluorescence varie avec la fixation de l’antigène, ce qui permet sa détection instantanée et quantitative. Nous avons cherché à obtenir des biocapteurs FA à partir de n'importe quelle ankyrine artificielle (Darpin). Des règles de conception ont été développées pour identifier les positions auxquelles un fluorophore pouvait être couplé, en présence ou absence de données structurales. Ces stratégies ont été validées pour deux Darpins dirigées contre la protéine MalE d’E. Coli. Pour améliorer les tests diagnostiques d’infections flavivirales, nous avons construit des bioconjugués entre le domaine 3 de la protéine d’enveloppe de plusieurs flavivirus et la phosphatase alcaline d’E. Coli. Nous avons évalué l’efficacité de 5 conjugués, correspondant aux 4 sérotypes du virus la Dengue (DENV1-4) et au virus de la Fièvre Jaune, dans nos tests simplifiés de MAC- et GAC-ELISA, pour 200 sérums humains. Les infections récentes étaient détectées par MAC-ELISA, avec une bonne sensibilité et spécificité, excepté pour DENV4.
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Rockstroh, Alexandra. "Entwicklung von Verfahren für die spezifische, serologische Diagnostik von Dengue- und Zika-Virusinfektionen mit modifizierten Envelope Proteinen." 2017. https://ul.qucosa.de/id/qucosa%3A31922.
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Das Dengue-Virus ist ein, in tropischen und subtropischen Regionen endemisches, humanpathogenes Virus, welches durch Moskitos des Genus Aedes übertragen wird. Jährlich werden ca. 95 Millionen der Infektionen klinisch manifestiert, wobei 1 % davon in der schwersten Form des Dengue-hämorrhagischen Fiebers verlaufen. Eine schnelle und einfache Diagnostik spielt dabei für die Behandlung sowie für epidemiologische Studien eine wichtige Rolle. Die serologische Diagnostik flaviviraler Infektionen im Allgemeinen und DENV im Speziellen, ist durch die Vielzahl kreuzreaktiver und infektionsverstärkender Antikörper hoch komplex. Die starke Co-Zirkulation verschiedener Flaviviren und deren ähnliche klinische Symptomatik erschwert zusätzlich die spezifische Diagnostik. Seit 2015 führte insbesondere der massive Vormarsch von ZIKV‑Infektionen in DENV-endemischen Gebieten Südamerikas zu einer noch komplexeren Sachlage, da die serologische Unterscheidung beider Infektionen kaum möglich war.
Im Rahmen dieser Promotionsarbeit wurden daher rekombinante virale E-Proteine exprimiert und charakterisiert, welche die Spezifität serologischer DENV- und ZIKV‑Tests erhöhen sollen. E-Proteine sind stark immunogen, da sie die Virusoberfläche dominieren. Jedoch ist deren hochkonservierte DII-FL Region gleichzeitig das Ziel von einem Großteil kreuzreaktiver Antikörper. Studien mit WNV und JEV haben zuvor belegt, dass Mutationen in diesem Sequenzbereich, die Kreuzreaktivität mit heterologen Flaviviren herabsenken können. Deshalb wurden vier Punktmutationen in die DII-FL Region von DENV 1-4 und ZIKV E (Equad) eingefügt und in einem Insektentenzellen- basierten System exprimiert, aus dem Kulturüberstand aufgereinigt und mit Humanseren in IgM- und IgG-ELISAs untersucht. Die Ergebnisse dieser Arbeit werden in zwei Publikationen dargelegt, welche die Grundlage für diese Promotionsschrift darstellen.
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"Design and Evaluation of a Non-Structural Protein 1-Based Diagnostic Zika Virus Infection." Tulane University, 2020.
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archives@tulane.eduZika virus (ZIKV), a member of the Flaviviridae family, was the cause of a large viral outbreak reaching across the Americas during 2015 and 2016. Discovered in 1947, it has historically been a neglected disease, due to its emergence in humans on a large scale being recent. At the time of the outbreak, no FDA approved ZIKV diagnostics existed, and those that were able to detect the virus were unable to distinguish it from related viruses such as Dengue virus (DENV), and at this time, no approved therapeutics or vaccines are available. We investigated the ability of diagnostics targeted toward both anti-NS1 antibodies and NS1 antigen circulating during infection to detect current or past ZIKV disease, as well as the capability of NS1 to produce a protective response. Our studies suggest anti-NS1diagnostics are feasible, though some populations may display an immune response reminiscent of a prior infection. Levels of circulating NS1 were lower than those produced during DENV infection, though were still detectable with our assay. Additionally, intraperitoneal immunization with NS1 produced an anti-ZIKV NS1 response that coincided with a decrease in viremia, though further work was needed to discern life-prolonging effects. Together, this work furthers the development of the tools necessary to combat future outbreaks of ZIKV in vulnerable populations.
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Brandon Beddingfield
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"Bispecific Antibodies for the Treatment of Co-Circulating Flaviviruses and Antibody Derivatives for Diagnostics in Checkpoint Immunotherapy." Doctoral diss., 2019. http://hdl.handle.net/2286/R.I.55649.
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abstract: Flaviviruses (FVs) are among the most medically important arboviruses of the world with the Dengue virus (DENV) accounting for a large percentage of infections observed in tropical and subtropical regions of the world. Globalization, travel, and the expanding range of mosquito vectors, such as Aedes aegypti, have increased the potential of infection rates and illnesses associated with FVs.
The DENV and the Zika (ZIKV) FVs frequently co-circulate and generally cause mild self-liming febrile illnesses. However, a secondary infection with a heterologous DENV serotype may lead to life threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). DHF/DSS have been linked to antibody dependent enhancement of infection (ADE), a phenomenon that occurs when antibodies (Abs) formed against an initial infection with one serotype of DENV cross-reacts but does not neutralize a heterologous DENV serotype in a secondary infection. Furthermore, Abs raised against the ZIKV have been observed to cross-react with the DENV and vice versa, which can potentially cause ADE and lead to severe DENV disease. The ZIKV can be transmitted vertically and has been linked to devastating congenital defects such as microcephaly in newborns. FDA approved treatments do not exist for DENV and ZIKV illnesses. Thus, there is a need for safe and effective treatments for these co-circulating viruses. Here, a tetravalent bispecific antibody (bsAb) targeting the ZIKV and all four serotypes of the DENV was expressed in the Nicotiana benthamiana (N. benthamiana) plant. Functional assays of the DENV/ZIKV bsAb demonstrated binding, neutralization, and a significant reduction in ADE activity against both the DENV and the ZIKV.
A single chain variable fragment (scFv) and a diabody based on an antibody directed against the immune checkpoint inhibitor PD-L1, were also expressed in N. benthamiana leaves. The smaller sizes of the scFv and diabody confers them with the ability to penetrate deeper tissues making them beneficial in diagnostics, imaging, and possibly cancer therapy. The past few decades has seen long strives in recombinant protein production in plants with significant improvements in production, safety, and efficacy. These characteristics make plants an attractive platform for the production of recombinant proteins, biologics, and therapeutics.Dissertation/Thesis
Doctoral Dissertation Molecular and Cellular Biology 2019
Books on the topic "Flavivirus diagnosis"
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Chambers, Thomas J. The Flaviviruses: Detection, Diagnosis and Vaccine Development. Burlington: Elsevier, 2003.
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Mesquita, Emersom C., and Fernando A. Bozza. Diagnosis and management of viral haemorrhagic fevers in the ICU. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780199600830.003.0293.
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In a globalized scenario where widespread international travel allows viral agents to migrate from endemic to non-endemic areas, health care providers and critical care specialists must be able to readily recognize a suspected case of viral haemorrhagic fever (VHF). Early suspicion is pivotal for improving patient outcome and to ensure that appropriate biosafety measures be applied. VHFs are acute febrile illnesses marked by coagulation disorders and organ specific syndromes. VHFs represent a great medical challenge because diseases are associated with a high mortality rate and many VHFs have the potential for person-to-person transmission (Filoviruses, Arenavioruses, and Bunyaviroses). Dengue is the most frequent haemorrhagic viral disease and re-emergent infection in the world and, due to its public health relevance, severe dengue will receive special attention in this chapter. The diagnosis of VHFs is made by detecting specific antibodies, viral antigens (ELISA) and viral nucleic acid (RT-PCR) on blood samples. Supportive care is the cornerstone in the treatment of VHFs. Ribavirin should be started as soon as a case of VHF is suspected and discontinued if a diagnosis of Filovirus or Flavivirus infection is established. Adjunctive antimicrobial therapy is usually implemented to treat co-existing or secondary infections. Antimalarial treatment should also be initiated if a malaria test (thick blood films) is not quickly available and/or reliable and patients travel history is compatible. It is always recommended to apply appropriate biosafety measures and notify local infection control unit and state and national authorities.
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Казачинская, Е. И. ВИРУС ДЕНГЕ. Академическое изд-во «Гео», 2021. http://dx.doi.org/10.21782/b978-5-6043022-6-2.
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The review is devoted to the analysis of literature data on the history research of dengue fever, the discovery of the etiological infectious agent of this disease-dengue virus and its serotypes. A taxonomic overview of the }lavivirus family, genome organization, structure and function of viral proteins, mosquito species-viral vectors and virus transmission cycles, theories of its origin are presented. As well as the evolution, characteristics and epidemiology of viral serotypes, cellular receptors for dengue virus penetration, pathogenicity for human and factors for the development of severe disease, induced immunity, applied methods and markers for diagnosis, principles of disease treatment and drug development (more information about monoclonal antibodies-potential therapeutic drugs), vaccine options and their effectiveness are considered. The book is intended for students, graduate students, employees of research institutions and universities, as well as doctors involved in the study of }laviviruses and the problem of differential diagnosis of flavivirus infections.
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The Flaviviruses: Detection, Diagnosis, and Vaccine Development. Elsevier, 2003. http://dx.doi.org/10.1016/s0065-3527(00)x0008-5.
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The Flaviviruses: Detection, Diagnosis and Vaccine Development, Volume 61 (Advances in Virus Research). Academic Press, 2003.
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Calisher, Charles H., and Thomas P. Monath. "Togaviridae and Flaviviridae: The Alphavirases and Flaviviruses." In Laboratory Diagnosis of Infectious Diseases Principles and Practice, 414–34. New York, NY: Springer New York, 1988. http://dx.doi.org/10.1007/978-1-4612-3900-0_22.
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Trent, Dennis W., and Gwong-Jen Chang. "Detection and Identification of Flaviviruses by Reverse Transcriptase Polymerase Chain Reaction." In Diagnosis of Human Viruses by Polymerase Chain Reaction Technology, 355–71. Berlin, Heidelberg: Springer Berlin Heidelberg, 1992. http://dx.doi.org/10.1007/978-3-642-84766-0_27.
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Alcon-LePoder, S., P. Sivard, M. T. Drouet, A. Talarmin, C. Rice, and M. Flamand. "Secretion of Flaviviral Non-Structural Protein NS1: from Diagnosis to Pathogenesis." In Novartis Foundation Symposia, 233–50. Chichester, UK: John Wiley & Sons, Ltd, 2008. http://dx.doi.org/10.1002/0470058005.ch17.
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W., Brett, and Charles E. "Human Rabies Epidemiology and Diagnosis." In Non-Flavivirus Encephalitis. InTech, 2011. http://dx.doi.org/10.5772/21708.
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Sá Teles de Oliveira Molina, Juliana, Andreia Moreira dos Santos Carmo, Gabriel Lopes Pereira, Leticia Abrantes de Andrade, Felipe Trovalim Jordão, Rodrigo Buzinaro Suzuki, Luana Prado Rolim de Oliveira, Aline Diniz Cabral, and Márcia Aparecida Sperança. "Novel Single Hematophagous Insect RNA Detection Method Supports Its Use as Sentinels to Survey Flaviviruses Circulation." In Dengue Fever in a One Health Perspective. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.92071.
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Anthropogenic actions, including deforestation, disorganized urbanization, and globalization, contribute to emergence and reemergence of arboviruses worldwide, where Flavivirus is the most prevalent, and its continuous monitoring can help in preventive control strategies. Thus, the aim of this study was to detect flavivirus RNA in single hematophagous insects, which are used as sentinels. Total RNA was extracted from six Aedes aegypti stored since 2003 and from 100 Culicidae and collected through CDC trap in a public park of a Brazilian Northwest city of São Paulo State. Flavivirus was detected through RT/PCR targeting 230–250 bp of the RNA polymerase coding sequence (NS5). PCR amplicons were sequenced by Sanger method, used in comparative analysis over Basic Local Alignment Search Tool (BLAST) in GenBank, and subjected to Neighbor-Joining phylogenetic analyses. Efficiency of Flavivirus diagnosis was confirmed by detection of Dengue virus serotype 2 in Ae. aegypti. From the 100 collected insects, 19 were positive for Culex flavivirus (CxFV). NS5 partial sequence phylogenetic analysis clustered all CxFV in one branch separated from vertebrate flaviviruses, being applicable to the identification of Flavivirus species. The dipteran RNA extraction methodology described in this work supports detection of flaviviruses in single insects maintained in 80% ethanol, which can be used to constant arbovirus surveillance.
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Svihrova, Viera, Henrieta Hudeckova, Janka Buchancova, and Maria Avdicov. "Analysis of the Incidence of Tick-Borne Encephalitis as an Occupational Disease and of the Costs of the Diagnosis and Treatment of Acute Tick-Borne Encephalitis in the Slovak Republic from 1989 to 2009." In Flavivirus Encephalitis. InTech, 2011. http://dx.doi.org/10.5772/20410.
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Burali, Maria Sole, and Giuseppe Manfroni. "Pyridobenzothiazolones as anti-flavivirus agents: Impact on Zika virus." In Zika Virus Impact, Diagnosis, Control, and Models, 349–58. Elsevier, 2021. http://dx.doi.org/10.1016/b978-0-12-820267-8.00033-9.
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Beatriz Borges Silva, Isaura, Renato Kaylan Alves de Oliveira França, Jacyelly Medeiros Silva, Andrea Queiroz Maranhão, and Carlos Roberto Prudencio. "Phage Display as a Strategy to Obtain Anti-flavivirus Monoclonal Antibodies." In Dengue Fever in a One Health Perspective. IntechOpen, 2020. http://dx.doi.org/10.5772/intechopen.93076.
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Arbovirus of the Flaviviridae family represents an issue worldwide, particularly because it can lead to serious illness and death in some countries. There is still a great complexity in obtaining effective therapies and specific and sensitive diagnostic tests, due to the high antigenic similarity between them. This similarity may account for antibodies cross reactivity which has positive and negative consequences for the course of infectious diseases. Among dengue virus (DENV) serotype infections, the cross-reactivity can increase virus replication and the risk of a severe disease by a mechanism known as an antibody-dependent enhancement (ADE). The search for serological biomarkers through monoclonal antibodies (MAbs) that identify unique viral regions can assist in the differential detection, whereas the development of recombinant antibodies with a neutralizing potential can lead to the establishment of efficacious treatments. The Phage Display methodology emerged as one of the main alternatives for the selection of human MAbs with high affinity for a specific target. Therefore, this technology can be a faster alternative for the development of specific diagnostic platforms and efficient and safe treatments for flavivirus infections. In this context, we propose for this chapter a discussion about Phage Display as a strategy to obtain MAbs for DENV and other flaviviruses.
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Ooi, E. E., L. R. Petersen, and D. J. Gubler. "Flaviviruses excluding dengue." In Oxford Textbook of Medicine, 564–75. Oxford University Press, 2010. http://dx.doi.org/10.1093/med/9780199204854.003.070514_update_001.
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Flaviviruses, family Flaviviridae, are enveloped viruses with a single-strand positive-sense RNA genome approximately 11 kb in length. They comprise 53 species (40 of which can cause human infection), divided into three major groups based on epidemiology and phylogenetics. They are maintained in nature in complex transmission cycles involving a variety of animals and hematophagous arthropods, which transmit infection to humans. IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) is widely used for diagnosis, with confirmation requiring a four-fold or greater rise in specific antibodies between acute and convalescent serum samples, virus isolation, detection of specific antigen by immunohistochemistry or of viral RNA by nucleic acid amplification from blood or other tissue sample....
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Silva, Breno de Mello, Cyntia Silva Ferreira, Túlio César Rodrigues Leite, Bruna de Paula Dias, Ricardo Lemes Gonçalves, Samara Mayra Soares Alves dos Santos, Camila Cavadas Barbosa, and Erica Milena de Castro Ribeiro. "NEW FLAVIVIRUS DIAGNOSTIC METHODS WITH GOLD NANOPARTICLES." In Ciências médicas: Campo teórico, métodos, aplicabilidade e limitações, 133–46. Atena Editora, 2021. http://dx.doi.org/10.22533/at.ed.91021080715.
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