Дисертації з теми "Flavivirus Infection"
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Gollins, S. W. "Mechanisms of flavivirus neutralization and cellular infection." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.355752.
Повний текст джерелаDejarnac, Ophélie. "Molecular and cellular basis of phosphatidylserine receptors mediated flavivirus infection." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC297/document.
Повний текст джерелаDengue virus (DENV) and ZIKA virus (ZIKV) are two mosquito-borne viruses responsible for important diseases in humans. Since there is currently no vaccine neither antiviral treatment available against these human pathogens, they are two major health concerns. The molecular basis of DENV and ZIKV host cell interactions leading to virus entry are poorly understood, hampering the discovery of new targets for antiviral intervention. Our laboratory recently discovered that TIM (TIM-1 and TIM-4) and TAM (Tyro3 and Axl) proteins, two receptor families that contribute to the phosphatidylserine (PtdSer)-dependent phagocytic removal of apoptotic cells, are DENV entry factors. TIM and TAM receptors mediate DENV infection by interacting with virion-associated PtdSer through a mechanism similar to the recognition and engulfment of apoptotic cells by phagocytes (viral apoptotic mimicry). The general objective of my PhD was to establish a detailed understanding of the molecular mechanisms by which TIM-1 and Axl mediated infection. Using live imaging, we demonstrated that TIM-1 and DENV are co-internalised and TIM-1 play an active role during DENV endocytosis. We showed that TIM-1 cytoplasmic domain is essential for DENV internalization, especially, we identified two lysine residues that are essential for TIM-1 ubiquitination and DENV endocytosis. Proteomic analysis of TIM-1 interacting partners identified STAM, a member of the ESCRT-0 complex involved in intracellular sorting of ubiquitinated cargos, as an essential host factor for DENV infection. Collectively our results establish TIM-1 as the first identified DENV bona fide receptor.Identifying ZIKV entry factors represents a major challenge in the understanding of ZIKV tropism and pathogenesis. We showed that Axl is responsible for ZIKV infection of microglial cells and astrocytes in the human developing brain and primary fibroblasts in human skin, suggesting an important role of this receptor during ZIKV life cycle. We also highlighted the dual role of the Axl receptor in ZIKV infection, which simultaneously promotes viral entry and dampens the innate immune response to facilitate a post entry step of the ZIKV life cycle. In conclusion, this work provided new insights in our understanding of the DENV and ZIKV entry program. Both viruses engage phospholipid receptors for their infectious entry, providing a rational to ascertain therapeutic strategies targeting virion-associated phospholipids
Nguyen, Jennifer B. "Molecular Mechanisms of Host-Pathogen Interactions in Flavivirus and Hookworm Infection." Thesis, Yale University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3580786.
Повний текст джерелаMicrobial pathogens and their hosts have evolved complex adaptations to ensure their individual survival, resulting in a so-called "molecular arms race." While hosts may have acquired diverse mechanisms to protect themselves from the microbial invader, pathogens have developed elaborate strategies to evade and subvert these defenses. Viruses and hookworms are important pathogens which have evolved to successfully invade and infect their human hosts. Although structural biology has provided significant mechanistic insight into these processes of invasion, many specific host-pathogen interactions and their dynamics have not been well studied or characterized.
The work presented in this dissertation clarifies the mechanisms of cellular entry of one particular family of viruses, the flaviviruses, and discusses strategies for viral clearance by host cells. Additional insight into the role of a cytoplasmic DNA sensor, LRRFIP1, in mediating an innate immune response to non-flavivirus microbial infection is presented. Finally, strategies for the development of small-molecule or peptide inhibitors of virus entry and hookworm infection are proposed.
Ottendorfer, Christy L. "Impact of West Nile virus on the natural history of St. Louis encephalitis virus in Florida." [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002452.
Повний текст джерелаDesole, Giovanna. "Comparative analysis of Zika virus and other Flavivirus infection in human neural cells." Doctoral thesis, Università degli studi di Padova, 2018. http://hdl.handle.net/11577/3424985.
Повний текст джерелаPresupposti dello studio: Zika virus (ZIKV), West Nile virus (WNV), dengue virus (DENV) e Usutu virus (USUV) sono trasmessi da zanzare ed appartengono al genere Flavivirus della famiglia Flaviviridae. L’infezione da ZIKV è associata a microcefalia fetale e sindrome di Guillan-Barrè; WNV può causare una grave sindrome neuroinvasiva nell’anziano e nei soggetti immunocompromessi; l’infezione da DENV raramente si associa a complicazioni neurologiche; USUV può causare una sindrome neuroinvasiva fatale in diverse specie di uccelli, è stato dimostrato che può infettare pure l’uomo, ma la sua patogenicità resta ancora da chiarire. Scopo: Alla luce della recente epidemia di ZIKV in America e di una probabile associazione tra l’infezione da ZIKV e lo sviluppo di microcefalia fetale, lo scopo di questo studio è stato confrontare l’infezione da ZIKV sulle cellule neurali umane con l’infezione da WNV, DENV e USUV. A tal fine, la cinetica di replicazione, l’effetto citopatico e l’immunità innata indotta dall’infezione virale sono state analizzate in cellule staminali pluripotenti indotte (hiPSCs), cellule staminali neurali derivate da iPSCs e neuroni. Materiali e metodi: Le NSCs ed i neuroni sono stati differenziati da hiPSCs. I diversi tipi cellulari sono stati infettati con l’isolato di ZIKV lignaggio asiatico (KU853013), WNV lignaggio 2 (KF179640), DENV sierotipo 2 e USUV lignaggio 1 europeo (AY453411). La carica virale è stata valutata a diversi tempi dall’infezione mediante qRT-PCR e TCID50, il livello di espressione dei geni coinvolti nell’immunità innata è stato analizzato mediante qRT-PCR e l’espressione dei markers di differenziamento cellulare mediante IF e qRT-PCR, la sopravvivenza cellulare e l’apoptosi mediante il saggio MTT e analisi dell’attivazione di caspasi-3. L’impatto dell’infezione da ZIKV sull’embriogenesi e la neurogenesi è stato valutato infettando le hiPSCs e le NSCs durante il differenziamento neurale e durante la formazione dei corpi embrioidi. Risultati: ZIKV era in grado di infettare e replicare efficientemente nelle NSCs, nei neuroni e nelle hiPSCs, causando un tipico effetto citopatico e morte cellulare per apoptosi. L’infezione ha indotto un significativo aumento dell’espressione dei geni dell’immunità innata, in particolare dei geni MDA5 (the cellular pattern recognition receptor (PRR) IFH1 gene), IFIT1 (IFN-induced protein with tetratricopeptide repeats 1) e IFIT2. I corpi embrioidi sono stati distrutti dal virus e le hiPSCs e le NSCs infettate sono morte prima di completare il differenziamento neurale. L’efficienza di replicazione di ZIKV nelle NSCs era maggiore rispetto a quella di DENV-2 e USUV, ma minore rispetto al WNV. Infatti, WNV replicava in modo più efficiente, induceva una maggiore morte cellulare e stimolava una più elevata risposta antivirale rispetto a ZIKV nei diversi tipi cellulari. Conclusione: ZIKV infetta e replica nelle NSCs, inducendo morte cellulare e impedendo lo sviluppo neurale, ma in modo meno efficiente rispetto al WNV. E’ probabile quindi che l’infezione di altri tipi cellulari sia determinante per il danno al sistema nervoso fetale indotto in modo specifico da ZIKV.
Rückert, Claudia. "Alphavirus and flavivirus infection of Ixodes tick cell lines : an insight into tick antiviral immunity." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/10063.
Повний текст джерелаYouseff, Brian. "The Role of Tumor Necrosis Factor Receptor-Associated Factor 6 in Tick-Borne Flavivirus Infection." University of Toledo Health Science Campus / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=mco155691388498993.
Повний текст джерелаPettersson, John H. O. "The Origin of the Genus Flavivirus and the Ecology of Tick-Borne Pathogens." Doctoral thesis, Uppsala universitet, Systematisk biologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-211090.
Повний текст джерелаCourtney, Sean C. "Functional Analysis of Host Cell Proteins and Stress Responses that Inhibit West Nile Virus Infection." Digital Archive @ GSU, 2011. http://digitalarchive.gsu.edu/biology_diss/101.
Повний текст джерелаRiccetti, Silvia. "In vitro modelling of patient-specific susceptibility to neurotropic flavivirus infection by using induced pluripotent stem cells." Doctoral thesis, Università degli studi di Padova, 2019. http://hdl.handle.net/11577/3422230.
Повний текст джерелаAsghar, Naveed. "Ticks and Tick-borne Encephalitis Virus : From Nature to Infection." Doctoral thesis, Södertörns högskola, Miljövetenskap, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:sh:diva-31153.
Повний текст джерелаVektorburna sjukdomar är ett växande globalt hot mot både människor och djur. De pågående klimatförändringarna kan leda till förhöjda risker för infektioner överförda av myggor, fästingar och andra leddjursvektorer. Ixodes ricinus är en vanlig fästing i Europa som överför fästingburna patogener som är farliga för människor. Fästingburen encefalit (TBE) är en vektorburen sjukdom som orsakas av TBE-virus (TBEV). De pågående klimatförändringarna har bidragit till en ökning både av vektorn och sjukdomsfrekvensen. Mellan 10 000 och 15 000 mänskliga TBE-fall rapporteras årligen i Europa och Asien. Den geografiska fördelningen av TBEV visar ett ojämnt fördelningsmönster där viruset är koncentrerat till vissa fokusområden. TBEV återfinns i naturen i en livscykel där viruset hela tiden överförs mellan fästingar och däggdjur. Spridningen sker dels från en infekterad fästing till ett ryggradsdjur när fästingen äter på värddjuret. Spridning mellan fästingar sker troligen främst genom så kallad “co-feeding”, det vill säga att flera fästingar suger blod samtidigt från samma värddjur. Viruset kan då passera från en infekterad fästing, genom värddjuret till oinfekterade fästingar. Virus kan identifieras och studeras med genetiska metoder. Det ökande antalet TBE-fall i Skandinavien styrker vikten av att hitta och karakterisera ytterligare TBEV-stammar och identifiera nya naturliga fokusområden. Vi har sekvenserat och fylogenetiskt beskrivit fyra TBEV-stammar: Saringe-2009 (blodfylld nymf), JP-296 (födosökande vuxen hane), JP-554 (födosökande vuxen hane) och Mandal-2009 (födosökande nymfer, n = 10). Mandal-2009 är ett TBEV från ett naturligt fokusområde i södra Norge. Saringe-2009 kommer från ett naturligt fokusområde i norra Stockholms län, Sverige. JP-296 och JP-554 härstammar från Torö som är ett naturligt fokusområde i södra Stockholms län, Sverige. Förutom den genetiska sekvenseringen av TBEV har vi också studerat effekten av olika biotiska och abiotiska faktorer på populationsdynamik av I. ricinus i södra Stockholm och observerade variation i fästingsaktivitetsmönster både temporalt och spatialt. Förekomstmönster av fästinglarver, nymfer och vuxna honor, och det totala antalet fästingar är viktiga faktorer för sannolikheten för horisontell överföring av TBEV mellan fästingar. Vi fann att sannolikheten för synkron förekomst av larver, nymfer och honor var högst under försommaren. Vegetationshöjd, mängden skog och mängd öppet vatten runt undersökningsområden hade signifikanta negativa effekter på sannolikheten för att larver, nymfer och honor skulle förekomma samtidigt. Den variabla delen av den icke-kodande 3 ́regionen (3'NCR) av TBEV-genomet innehåller ofta en intern poly(A)-sekvens. Liksom andra RNA-virus, förekommer TBEV som så kallade ”quasispecies” vilka definieras som grupper av olika genetiska varianter av virus. Genom analysen av TBEV-stam Saringe-2009 avslöjades variation i poly(A)-sekvensen vilket indikerar förekomst av ”quasispecies”. Eftersom Saringe-2009 kom från en blodfylld nymf som hade sugit blod i > 60 timmar, föreslår vi att Saringe-2009 visar en förändring i ”quasispecies”-poolen när viruset överförs från exoterm fästingmiljö till endoterm däggdjursmiljö. Vi undersökte poly(A)-ekvensens variabilitet och dess roll vid replikering och för virulens hos TBEV, genom att skapa två infektiösa kloner av Torö-2003 stammen; en med en kort/vild-typ (A)3C(A)6 poly(A)-sekkvens, och en med en lång (A)3C(A)38 poly(A)-sekvens. Den infektiösa klonen med lång poly(A)-sekvens replikerade sämre än vildtypklonen i cellkultur, men (A)3C(A)38 poly(A) var mer virulent i C57BL/6-möss än (A)3C(A)6 poly(A). Datasimulering av TBEV-genomets sekundär-RNA-struktur visade att de längre poly(A)-sekvenserna påverkar veckningen av en specifik sekundärstruktur (SL14) i början av 3 ́NCR. Djupsekvenseringsanalys av TBEV-gnomen avslöjade skillnader för specifika gener och ”quasispecies”-strukturen efter passering i cellkultur och/eller mushjärna. Dessa förändringar föreslås bidra till de observerade skillnaderna i virulens. Våra resultat indikerar att den långa poly(A)-sekvensen ger instabilitet i TBEV-genomet, vilket resulterar i ökad mångfald av ”quasispecies”-populationen som i sin tur kan bidra till TBEV-virulens. Fylogenetisk analys av Saringe-2009, JP-296, JP-554 och Mandal-2009 visade på ett nära släktskap mellan de fyra skandinaviska TBEV-stammarna. De nya stammarna formerade ett kluster med en tidigare TBEV-stam identifierad på Torö (Toro-2003), vilket skapade ett skandinaviskt klad. Genetisk analys visade att Mandal-2009 innehåller en trunkerad 3 ́NCR som liknar den högvirulenta stammen HYPR. JP-296 och JP-554 hade däremot samma genetiska struktur som den längre Torö-2003 stammen från samma fokusområde. Djupsekvensering visade höge mångfald av ”quasispecies”-populationen för JP-296 och JP- 554 jämfört med Mandal-2009. Analys av enkel nukleotid polymorfism (SNP) visade att 40 % av alla SNP var gemensamma mellan ”quasispecies”-populationen för JP-296 och JP-554. Detta indikerar att TBEV-”quasispecies”-strukturen kan vara konserverad för närbesläktade virus vilken kan leda till att den bevaras inom specifika fokusområden. Sammantaget så visar dessa studier att miljöfaktorer påverkar förekomsten av fästingvektorn och dess olika livsstadier, vilket är en bakomliggande faktor för utbredning av TBEV i naturliga fokusområden. Det visar även på att värdmiljön påverkar strukturen för ”quasispecies”-populationen. Dessutom visar våra studier att evolution och utveckling av ”quasispecies”-strukturen kan påverka virulensen för TBEV i möss.
Pinho, dos Reis Vinícius [Verfasser], Rainer G. [Akademischer Betreuer] Ulrich, Martin H. [Akademischer Betreuer] Groschup, Markus [Akademischer Betreuer] Keller, Rainer G. [Gutachter] Ulrich, and Stefanie [Gutachter] Becker. "The role of integrins in flavivirus infection / Vinícius Pinho dos Reis ; Gutachter: Rainer G. Ulrich, Stefanie Becker ; Rainer G. Ulrich, Martin H. Groschup, Markus Keller." Greifswald : Ernst-Moritz-Arndt-Universität, 2019. http://d-nb.info/117724151X/34.
Повний текст джерелаReis, Vinicius Pinho dos [Verfasser], Rainer G. [Akademischer Betreuer] Ulrich, Martin H. [Akademischer Betreuer] Groschup, Markus [Akademischer Betreuer] Keller, Rainer G. [Gutachter] Ulrich, and Stefanie [Gutachter] Becker. "The role of integrins in flavivirus infection / Vinícius Pinho dos Reis ; Gutachter: Rainer G. Ulrich, Stefanie Becker ; Rainer G. Ulrich, Martin H. Groschup, Markus Keller." Greifswald : Ernst-Moritz-Arndt-Universität, 2019. http://d-nb.info/117724151X/34.
Повний текст джерелаReis, Vinicius Pinho dos [Verfasser], Rainer G. [Akademischer Betreuer] Ulrich, Martin H. [Akademischer Betreuer] Groschup, Markus [Akademischer Betreuer] Keller, Rainer G. Gutachter] Ulrich, and Stefanie [Gutachter] [Becker. "The role of integrins in flavivirus infection / Vinícius Pinho dos Reis ; Gutachter: Rainer G. Ulrich, Stefanie Becker ; Rainer G. Ulrich, Martin H. Groschup, Markus Keller." Greifswald : Ernst-Moritz-Arndt-Universität, 2019. http://d-nb.info/117724151X/34.
Повний текст джерелаIzuogu, Adaeze O. Izuogu. "Restriction of tick-borne flaviviruses in the white-footed mouse." University of Toledo Health Science Campus / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=mco1501786858639212.
Повний текст джерелаMcAtamney, Sarah. "Investigation of Dengue Fever Virus Envelope Glycoprotein Carbohydrate-Ligand Recognition Events Essential for Mammalian Cell Infection." Thesis, Griffith University, 2009. http://hdl.handle.net/10072/366363.
Повний текст джерелаThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
Institute for Glycomics
Full Text
Grard, Gilda. "Génomique et évolution des flavivirus transmis par les tiques et découverte d'un nouveau lignage du genre flavivirus." Aix-Marseille 2, 2006. http://www.theses.fr/2006AIX20679.
Повний текст джерелаScaramozzino, Natale. "Flavivirus : étude d'une cible diagnostique, la région NS codant pour la polymérase et d'une cible thérapeutique, la protéase NS3 du virus Langat." Université Joseph Fourier (Grenoble), 2002. http://www.theses.fr/2002GRE19004.
Повний текст джерелаFlaviviruses are responsible for considerable morbidity and mortality and may cause severe encephalitis, hemorrhagic fever, hepatitis, and febrile symptoms in vertebrates, including humans (. . . ). Different p-nitroanilide substrates, defined on canonic sequences for their susceptibility to Ser-protease, were applied to the proteolytic assays of the protein. The highest values were obtained from substrates containing an Arg or Lys (amino acid) residue at the P1 position. This purification method will facilitate the future development of reliable testing procedures for anti-proteases directed to NS3 proteins
Defrocourt, Christophe. "L'encéphalite japonaise en 2003 : épidémiologie et nouvelles perspectives de vaccin." Rouen, 2004. http://www.theses.fr/2004ROUEP008.
Повний текст джерелаTerrien, Vincent Alliot Anne. "Les culicidés transmission vectorielle des infections et parasitoses à l'homme /." [S.l.] : [s.n.], 2008. http://castore.univ-nantes.fr/castore/GetOAIRef?idDoc=46631.
Повний текст джерелаRechoum, Yassine. "Détection de séquences d'ARN du VHC dans des extraits de moustiques du genre Aedes : étude cinétique après infections expérimentales." Grenoble 1, 2009. http://www.theses.fr/2009GRE10205.
Повний текст джерелаLn order to explore the ability of mosquitoes to replicate HCV, we conducted a series of experimental infections caspius on Aedes, Aedes vexans and Culex pipiens wild and farmed. After collection of mosquitoes, the females were fed a blood meal viremic (HCV 1b positive). The mosquitoes were th en maintained in breeding for several days. After development of detection conditions, we were able to demonstrate HCV repli cation in the mosquito Aedes vexans. Ln the first experimental infection performed on Ae. Vexans, we detected HC' RNA in - 50% of mosquitoes 21st days post-infection (JPI), PCR end point. The second infection experiment, conducted on Iwo types of mosquitoes: Aedes SP, and Culex pipiens, has allowed us to: (i) confirmation by qRT-PCR results of the first experience with an infection rate of - 33%, (ii) demonstrate that only the mosquito Aedes contained RNA HCV, the Culex mosquitoes were ail negative, (iii) show that the RNA detected was good of replication, the extent of adaptive mutations were identified in the sequence of the RdRp (RNA polymerasi RNA dependent), with specificity for the genus Aedes, since ail Culex mosquitoes at 21 YPI were HCV RNA-negative. Another way to distinguish RNA from the replication of RNA remaining was to show the existence of a release within the mosquito. To do this, we conducted a third experiment infections (gender Ae. Caspius and Ae. Vexans), over a'period of 15 days and analyzed the presence of HCV RNA in distinct heads and bodies. Ln conducting samples at different times after infection (0, 4, 8 and 15 days), we managed to obtain a kinetic infection separately in heads and bodies, detection performed by WTA (Whole transcriptomics Amplification) followed by qPCR. On the day of infection (DO), the infection rate in the heads and bodies of mosquitoes was 9. 1 % and 100% respectively, the rate rose to 57. 1% and 85. 7% respectively J15 negativity after eight days after infection. On the other hand, we have identified mutations in th adaptation of the IRES sequence of mosquito D15 compared to those on day O. It is interesting to note that mosquito-positive HCV RNA ail belonged to the species vexans, showing that replication is species specific. Different regions of the HCV genome, then, were amplified. Finally, we made use of mosquito breeding. Infection of this strain has also shown, using different approaches to detection (qRT-PCR, qPCR-WTA, including HCV-GA), only 30 JPI, HCV RNA was present in - 33% heads and - 66% of the body, while infection rates were JO - 28% - 71 % in the head and body respectively. The results were based on sequencing performed on the amplified region! of the HCV genome. Ali these results show that HCV is able to replicate in mosquitoes of the genus Ae. Vexans, suggesting that HCV, likt other flaviviruses, can alternate belween Iwo hosts (primates and mosquitoes) and has lost its potential for replication in the mosquito ove time
Bessaud, Maël. "Etude in vitro du complexe protéasique [NS2B/NS3] des flavivirus, cible potentielle de molécules antivirales." Aix-Marseille 2, 2005. http://theses.univ-amu.fr.lama.univ-amu.fr/2005AIX22027.pdf.
Повний текст джерелаBrandler, Samantha. "Etude du mécanisme d'inhibition de la fusion des flavivirus par les anticorps et mise au point d'un candidat vaccin contre la dengue basé sur l'expression d'un antigène d'enveloppe par un vecteur dérivé du vaccin contre la rougeole." Aix-Marseille 1, 2008. http://theses.univ-amu.fr.lama.univ-amu.fr/2008AIX11003.pdf.
Повний текст джерелаDengue fever is a reemerging disease that threatens one third of the world's population, for which no vaccine is available. In this work, we evaluated a new vaccination strategy based on the expression of a combined dengue antigen by a vector derived from the pediatric live attenuated measles vaccine. Understanding the mechanisms of flavivirus neutralization by antibodies is essential for the design of innovative vaccine approaches against dengue. Therefore, as a first step, we studied the mechanism of inhibition of fusion by neutralizing antibodies directed against the three domains of the envelope protein (E). The Tick-borne encephalitis virus (TBEV) was used as a model in in vitro fusion tests, and coflottation assays with lipid membranes. The results showed that the neutralizing antibodies can interfere with the early or late stages of the fusion process. This study also shows that antibodies against domain III of the E protein can block both the viral entry and fusion. As a proof-of-concept of our vaccination strategy, we inserted into measles vector the domain III of the glycoprotein E of dengue virus (EDIII), which contains the putative receptor binding site and serotype-specific neutralizing epitopes. To strengthen its immunogenicity, EDIII was fused with the pro-apoptotic ectodomain of the membrane protein (ectoM) of VDEN-1. Tested in mice susceptible to measles, this vaccine candidate was immunogenic and able to induce long term serotype-specific neutralizing antibodies. The presence of the ectoM proved crucial for the immunogenicity of EDIII. Its adjuvant capacity correlated with its ability to mature dendritic cells and to enhance the secretion of proinflammatory and antiviral cytokines, as well as chemokines involved in the development of adaptive immunity. A tetravalent measles-dengue candidate was then generated in order to induce the same immunity against the 4 serotypes of dengue virus. This vaccination strategy combining measles and dengue might offer an affordable pediatric vaccine particularly attractive to immunize children both against measles and dengue fever in areas of the world where the two diseases co-exist
Michel, Friederike [Verfasser]. "Monitoring and pathogenesis of flavivirus infections in wild birds and domestic poultry in Germany / Friederike Michel." Hannover : Stiftung Tierärztliche Hochschule Hannover, 2019. http://d-nb.info/1201644364/34.
Повний текст джерелаKles, Virginie. "Contribution à l'étude des arboviroses sur l'Ile de la Réunion : enquête séro-épidémiologique." Brest, 1993. http://www.theses.fr/1993BRES2027.
Повний текст джерелаArnal, Audrey. "Circulation d'agents pathogènes en populations naturelles : approches éco-épidémiologiques chez le Goéland leucophée (Larus michaellis)." Thesis, Montpellier 2, 2012. http://www.theses.fr/2012MON20139/document.
Повний текст джерелаThe emergence of zoonotic diseases is directly linked to the noise generated by humans on the natural environment to a greater or lesser extent. Of all the emerging zoonoses in humans, the majority comes from wild animals. The study of the role of wildlife in the circulation of pathogens is crucial, especially when wildlife/human interfaces are prominent. The aim of this thesis is to understand, using large scale eco-epidemiological approaches, the circulation of pathogens in a close to human population of wild bird, the yellow-legged gull (Larus michahellis). The first chapter presents the different methods used in the monitoring of pathogens and their limitations when they are conducted in natural populations. This chapter further highlights, through a study of avian influenza viruses, that the quantification of maternal antibodies in eggs is an effective tool. The second chapter expands the spatial scale of the study to highlight the finer eco-epidemiological factors influencing the transmission of avian influenza viruses within and between populations of Western Mediterranean yellow-legged gull. Finally, the last chapter is based on the comparison of exposition patterns obtained for vectorial transmission mode pathogens: flaviviruses. This thesis highlights patterns of exposure for certain pathogens (avian influenza virus and flaviviruses) and enables the understanding of the eco-epidemiological factors potentially involved in their circulations. The results allow to consider future areas of research needed to more accurately assess the dispersion of these viruses over the Mediterranean
Baidaliuk, Artem. "Interactions between the insect-specific flavivirus CFAV, its mosquito host aedes aegypti, and co-infecting arboviruses." Electronic Thesis or Diss., Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2019SORUS494.pdf.
Повний текст джерелаDengue virus (DENV) and Zika virus (ZIKV) are mosquito-borne viruses that cause major public health problems worldwide. These arthropod-borne viruses (arboviruses) are RNA viruses of the Flavivirus genus that are primarily transmitted among humans by the mosquito Aedes aegypti. In addition, Ae. aegypti mosquitoes are naturally infected with cell-fusing agent virus (CFAV), the first-described insect-specific flavivirus (ISF). Little is known about CFAV evolution, interactions with arboviruses in coinfected mosquitoes, and mosquito immune responses to CFAV. This PhD work addressed such understudied aspects of CFAV biology. First, novel full-genome sequences of CFAV allowed a global phylogenetic analysis. A lack of phylogenetic congruence between CFAV and Ae. aegypti indicates that other factors than host population structure shape CFAV genetic diversity. Second, in coinfection experiments, CFAV inhibited DENV and ZIKV replication in vitro and their dissemination in vivo. These results support the hypothesis that ISFs may reduce arbovirus transmission in nature. Third, a CFAV-derived endogenous viral element (EVE) in the Ae. aegypti genome was found to regulate CFAV replication in the ovaries through the piRNA pathway. This finding suggests that EVEs may help to minimize reproductive costs associated with infection by cognate viruses. Overall, this PhD thesis shed light on the complex interactions between CFAV, Ae. aegypti, and arboviruses
CARLETTI, TEA. "The Unfolded Protein Response is required early during TBEV infection to trigger the interferon response." Doctoral thesis, Università degli Studi di Trieste, 2016. http://hdl.handle.net/11368/2908030.
Повний текст джерелаBeck, 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.
Повний текст джерелаFlaviviruses 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
Bates, Tyler Alexander. "Usutu Virus: An Emerging Arbovirus Threat." Thesis, Virginia Tech, 2021. http://hdl.handle.net/10919/102268.
Повний текст джерелаMaster of Science
Usutu virus (USUV) is an emerging mosquito-borne virus that was first isolated from a mosquito in 1959 in South Africa, and since then, has become a major problem throughout Africa and Europe causing acute to severe infection in dozens of patients. Additionally, this virus is causing massive die-offs in Eurasian blackbird populations. This is particularly problematic because birds play a critical role in ecosystems as they act as forms of pest control, pollinators, and seed dispersers. Depletion of these species could lead to an imbalance and, eventually, collapse of our natural ecosystem. Additionally, there is a growing concern of USUV making its way into the United States, following a similar track of emergence to WNV's introduction in New York in 1999 and its subsequent spread throughout the states. WNV's introduction to the United States was detrimental to native bird populations and humans, and has caused tens of thousands of infections and thousands of deaths since this introduction. Research has shown USUV causes similar disease symptoms to WNV. The self-limiting illness from these viruses typically includes fever and rashes but some infections can result in more severe cases causing inflammation of the brain and surrounding areas. Like many other prominent mosquito-borne viruses, there is no specific treatment or vaccine for WNV or USUV. Because USUV is so closely related to WNV, and their similar characteristics may point towards similar emergence in the United States, it is essential to garner more information on USUV. The overall goal of this thesis was to establish a reliable tool(s) for further characterization of USUV and demonstrate the potential for USUV emergence in the United States. We first developed molecular tools, known as viral clones, that are valuable to the scientific community which allows the manipulation of USUV genetic material to perform further downstream studies. Our objective for this initial study was to create a molecular tool that would behave similarly to their natural, or "parental", virus. The results from this study suggest we have successfully produced these tools. Furthermore, we sought to determine the potential for field-caught mosquitoes from Southwest Virginia, USA to transmit a recently isolated strain of USUV. These data suggest that while these mosquitoes do have the ability to become infected with USUV, they have a limited potential to transmit this virus to animal hosts. Altogether, these studies have allowed us to expand our knowledge on USUV's potential emergence in the United States and develop powerful tools to continue this essential research.
Frank, Jordan C. "Development and Application of a Reverse Genetics System for Zika Virus." DigitalCommons@USU, 2018. https://digitalcommons.usu.edu/etd/7280.
Повний текст джерелаKortenhoeven, Cornell. "Genomics of West Nile viruses from South Africa." Diss., University of Pretoria, 2013. http://hdl.handle.net/2263/32944.
Повний текст джерелаDissertation (MSc)--University of Pretoria, 2013.
gm2013
Zoology and Entomology
Unrestricted
Zidane, Nora. "Remaniements rationnel de la protéine d'enveloppe virale et de ses domaines pour la détection des infections à flavivirus et l'étude d'interactions avec ses récepteurs." Paris 7, 2013. http://www.theses.fr/2013PA077149.
Повний текст джерелаThe envelope protein of Flaviviruses includes 3 ectodomains and a membrane segment. I have characterized the properties of its domain III (ED3) in vitro. I measured the thermodynamic stability of ED3 by experiments of unfolding equilibria, chemically or thermically induced and monitored by spectrofluorimetry; increased the stability of ED3 by changes of residues in its hydrophobic core without affecting its antigenicity; and showed that an ED3 domain, consensus for all the dengue viruses (DENV), was highly stable. The human Ribosomal Protein SA (RPSA) includes a folded N-terminal domain and a disordered C-terminal domain. We quantified their interactions with the ED3 domains of pathogenic Flaviviruses, laminin, heparin and an anticarcinogen (EGCG) by immunochemical and spectrofluorimétrie methods in vitro. I showed that the N- and C-domains had both idiosyncratic and shared fonctions, and that the C-domain mimicked heparin. We determined the serotype specificity of IgMs that were directed to the ED3 domain of each serotype of DENV by using DENV-infected or -uninfected human serums and a statistical analysis by receiving operator characteristic (ROC) curves. These serums were tested in MAC-ELISA with the 4 serotypes of a dimeric hybrid between ED3 and E, coli alkaline phosphatase. The discrimination by ED3 between serums infected by the homotypic DENV and uninfected serums varied with the serotype; it was maximal with the ED3 from DENV1 whatever the infecting serotype. Some ED3 domains discriminated between sérotypes of DENV. Potential applications are described
Baronti, Cécile. "Etude de Flavivirus : epidémiologie moléculaire en Bolivie et Analyse de leur interaction sur la réponse interféron dépendante du TLR3." Thesis, Aix-Marseille 2, 2010. http://www.theses.fr/2010AIX20664/document.
Повний текст джерелаThe Flavivirus genus consists of sevevral human pathogens responsible for hemorragic syndrome or encephalitis. The absence of specific antiviral treatment and an increase in Flavivirus incidence has led to a greater research effort in fighting these diseases. The study takes an epidemiological and a fundamental approach in its analysis of the innate immune response to flavivirus infection as well as flaviviral adaptation to evade this response. The analysis of circulating strains in Bolivia has led to a better understanding of dengue and yellow fever and also an awareness of their genetic variability. Given the limited information available in Bolivia, our studies could be used as a reference to understand future epidemics, improve diagnostic methods and allow the development of prevention strategies to fight against yellow fever in south Africa. The relationship between virus and host results from a subtle balance between viral replication and immunity clearance allowing the survival of both species. Each one as developed defence mechanisms against the other. We also examined the role of the non structural protein NS1 in the interferon respons to Flaviviral infection. Knowledge on viral escape strategies from host immunity could help to develop antiviral treatment for these arbovirus diseases
Grillo, Elena. "Presence of Haemosporidia and Flaviviruses in Breeding Prothonotary Warblers (Protonotaria citrea): An Analysis of Spatial and Temporal Trends in Infection Prevalence and Associations with Reproductive Success." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1857.
Повний текст джерелаFares, Mazigh. "Modélisation pathologique de l'infection par le virus de l'encéphalite à tiques et réponse antivirale induite dans les neurones et astrocytes dérivées de progéniteurs neuraux foetaux humains." Thesis, Paris, Institut agronomique, vétérinaire et forestier de France, 2018. http://www.theses.fr/2018IAVF0025.
Повний текст джерелаTick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, genus Flavivirus, is, from a medical point of view, the most important arbovirus in Europe and North-East Asia. It is responsible for febrile illness and, in some cases, for neurological manifestations ranging from mild meningitis to severe encephalomyelitis that can be fatal. Despite its medical importance, TBEV-induced neuropathogenesis remains poorly understood. Here, we used human neural cells differentiated from fetal neural progenitor cells (hNPCs) to model the infection in vitro and to decipher the mechanisms by which the virus damages the human brain. Our results showed that neurons and glial cells, namely astrocytes and oligodendrocytes, were permissive to TBEV. Neurons were massively infected and subjected to a dramatic cytopathic effect (60% loss 7 days post-infection). Astrocytes were also infected, although at lower levels, and the infection had a moderate effect on their survival (30% loss 7 days post infection), inducing a hypertrophied morphology characteristic of astrogliosis. Thus, two major cellular events described in TBEV-infected human brain (i.e. neuronal loss and astrogliosis) were reproduced in this in vitro cellular model, showing its relevance to study TBEV-induced neuropathogenesis. We therefore used it to tackle TBEV induced antiviral response. Using PCR arrays, we first showed that TBEV induced a strong antiviral response characterized by the overexpression of viral sensors, cytokines and interferon-stimulated genes (ISGs). Then, setting up enriched cultures of human neurons and human astrocytes, we further showed that the two cellular types were participating in the global antiviral response. However, astrocytes developed a stronger antiviral response than neurons. These results, by demonstrating that human neurons and human astrocytes have unique antiviral potential, suggest that their particular susceptibility to TBEV infection is due to their different capacity to mount a protective antiviral response
Jansson, Anna M. "Targeting Infectious Disease : Structural and functional studies of proteins from two RNA viruses and Mycobacterium tuberculosis." Doctoral thesis, Uppsala universitet, Struktur- och molekylärbiologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-196623.
Повний текст джерелаHoué, Vincent. "Characterization of non-retroviral integrated RNA virus sequences (NIRVS) in Aedes albopictus populations and Relation with vector competence." Electronic Thesis or Diss., Sorbonne université, 2019. http://www.theses.fr/2019SORUS139.
Повний текст джерелаAedes albopictus is a vector for transmitting arboviruses and this makes it a serious threat. In the last decade, NIRVS (non-retroviral integrated RNA virus sequences) from insect-specific flaviviruses (ISFs) have been found integrated in Aedes albopictus mosquito genome a long time ago. Moreover, it has been shown that these elements may have an antiviral role in vectors by producing piRNAs that would reduce viral replication. Here we characterized 7 NIRVS in 12 Aedes albopictus wild populations. We show that there is a high diversity inter- and intra-population, suggesting a complex evolution of these NIRVS in Aedes albopictus genome. Moreover, microsatellite analysis based on those same populations revealed that those NIRVS evolved differently from neutral genes, suggesting a potential function of these elements. We show that this function may be linked to the vector competence of Aedes albopictus to arboviruses, but remains unclear and require more investigations. Finally, we show by establishing persistent infected cells that NIRVS formation is an event that occurs rarely in the Aedes mosquito genome, and that arboviruses, along with ISFs, are also capable of endogenization in mosquitoes
Lourenço, José. "Unifying the epidemiological, ecological and evolutionary dynamics of Dengue." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:cb4db8dd-5467-4c6e-8d3e-3e0fe738bc0a.
Повний текст джерелаMiot, Elliott. "Potential of the mosquito Aedes malayensis as an arbovirus vector in South East Asia." Electronic Thesis or Diss., Sorbonne université, 2019. http://www.theses.fr/2019SORUS548.
Повний текст джерелаMany emerging arthropod-borne viruses (arboviruses) such as dengue virus (DENV) and yellow fever virus (YFV) originated in sylvatic cycles and have emerged among humans through spillover transmission by mosquito species that ‘bridge’ sylvatic and human transmission cycles. These bridge vectors can also mediate ‘spillback’ transmission of arboviruses from humans into novel sylvatic cycles. This PhD focused on Aedes malayensis, a mosquito species widely distributed in South East Asia, to assess its potential as an arbovirus vector. We identified Ae. malayensis for the first time in Laos during mosquito surveys conducted in a forested area of the Nakai Nam Theun National Protected Area (NNT NPA). Using field-based human-baited traps, we found that Ae. malayensis engaged in human-biting behavior and therefore could act as bridge vector in the NNT NPA. In laboratory conditions, this sylvatic population of Ae. malayensis displayed a relatively low vector competence for DENV and YFV and a lack of detectable attraction to human odor. However, vector competence assays and a human-baited trap survey showed that a peridomestic Ae. malayensis population in Singapore was competent for YFV and engaged in contact with humans. Overall, this PhD work highlighted that ancillary vectors should not be overlooked to fully assess the risk of arbovirus emergence
Uren, M. F. "Helper T cells in flavivirus infection." Phd thesis, 1987. http://hdl.handle.net/1885/142617.
Повний текст джерелаLin, Chi-Ping, та 林啟平. "To Study the Role of eIF2α Phosphorylation in Flavivirus Infection". Thesis, 2014. http://ndltd.ncl.edu.tw/handle/tp99ew.
Повний текст джерела國防醫學院
微生物及免疫學研究所
102
Japanese encephalitis virus (JEV) and dengue virus (Den) are flaviviruses whose genome is a single-stranded, positive-sense RNA with 5’ cap but without 3’ poly-A tail. After viral entry and uncoating, translation of flaviviral RNA is initiated by the host mRNA translation machineries. Cellular cap-dependent mRNA translation is tightly controlled by phosphorylation of eukaryotic initiation factor 2 α subunit (eIF2α) at residue Ser51. In response to certain stress condition, eIF2α can be phosphorylated by at least four different cellular kinases, for example PKR activated by dsRNA and PERK activated by endoplasmic reticulum stress, to temporally shut down cellular protein synthesis. Our previous studies indicate that JEV NS2A can block PKR-mediated eIF2α phosphorylation and eIF2α phosphorylation was only noted at late stage of JEV infection. To directly address the role of eIF2α phosphorylation in flavivirus infection, we manipulated the cellular eIF2α phosphorylation level by overexpressing eIF2α-S51D or -S51A mutants, mimicking the phosphorylated and unphosphorylated forms of eIF2α, respectively, and by treatment with an inhibitor of eIF2α de-phosphorylation, Salubrinal, which sustains endogenous eIF2α in phosphorylated status. JEV and Den-2 replication were suppressed in cells with eIF2α-S51D overexpression and in cells treated with Salubrinal. However, cells with eIF2α-S51A overexpression did not affect JEV and Den-2 replication. Thus, eIF2a phosphorylation play an antiviral role in flavivirus infection.
Chang, Tsung-Hsien, and 張聰賢. "The Mechanisms of Interferon-beta Gene Expression Induced by Flavivirus Infection." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/88203434422341098905.
Повний текст джерела國防醫學院
生命科學研究所
93
In this study, we found that infection with flaviviruses, such as Japanese encephalitis virus (JEV) and Dengue virus serotype 2 (DEN-2), leads to interferon-beta (IFN-beta) gene expression in a virus-replication- and de novo protein-synthesis-dependent manner. NF-kappa B activation is essential for IFN-beta induction in JEV- and DEN-2-infected cells. However, these two viruses seem to preferentially target different members of the interferon regulatory factor (IRF) family. The activation of constitutively expressed IRF-3, characterized by slower gel mobility, dimer formation, and nuclear translocation, is more evident in JEV-infected cells. Other members of the IRF family, such as IRF-1 and IRF-7 are also induced by DEN-2, but not by JEV infection. The upstream molecules responsible for IRF-3 and NF-kappa B activation were further studied. Evidently, a cellular RNA helicase, retinoic acid-inducible gene I (RIG-I), and a cellular kinase, phosphatidylinositol-3 kinase (PI3K), are required for flavivirus-induced IRF-3 and NF-kappa B activation, respectively. Therefore, we suggest that JEV and DEN-2 initiate the host innate immune response through a molecular mechanism involving RIG-I/IRF-3 and PI3K/NF-kappa B signaling pathways.
Chien, Hsuling, and 簡旭伶. "The roles of host cellular RNA-binding proteins on flavivirus infection." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/68947129120918829837.
Повний текст джерела國防醫學院
生命科學研究所
100
The untranslated regions (UTRs) located at the 5and 3 ends of the Japanese encephalitis virus (JEV) genome, a positive-sense RNA, are involved in viral translation, the initiation of RNA synthesis, and the packaging of nascent virions. The cellular and viral proteins that participate in these processes are expected to interact with the UTRs. In this study, we used biotinylated RNA-protein pulldown and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analyses to identify that the far upstream element (FUSE) binding protein 1 (FBP1) binds with JEV 5 and 3 UTRs. The impact of FBP1 on JEV infection was determined in cells with altered FBP1 expression. JEV replication was enhanced by knockdown and reduced by the overexpression of FBP1, indicating a negative role for FBP1 in JEV infection. FBP1, a nuclear protein, was redistributed to the perinuclear region and appeared as cytoplasmic foci that partially colocalized with JEV RNA in the early stage of JEV infection. By using a JEV replicon reporter assay, FBP1 appeared to suppress JEV protein expression mediated by the 5 and 3UTRs. Thus, we suggest that FBP1 binds with the JEV UTR RNA and functions as a host anti-JEV defense molecule by repressing viral protein expression. FBP1 was found to partially colocalize with stress granules (SGs) in JEV-infected cells and some viruses have been found to interact with the SG pathway. We thus study the role of SG in JEV infection. We found that JEV infection induced SGs formation and did not interfere with SG induction triggered by sodium arsenite stimulation. JEV- and Dengue virus serotype 2 (DEN-2)-induced SGs formation can not be blocked by specific inhibitors Y-27632 and Toxin B that inactive signaling of RhoA and its downstream kinase ROCK1, respectively, suggesting that RhoA/ROCK1 pathway is not involved in SGs induction during JEV and DEN-2 infection. In addition, monocyte chemotactic protein-induced protein 1 (MCPIP1), also known as Zc3h12a, could block the assembly of SGs in cells infected with JEV and DEN-2. Furthermore, several viral proteins such as core, prM, E, NS1, NS2B, NS4A, and NS4B, but not NS2B3 and NS5 are able to trigger SG formation . Overall, we demonstrate that SGs formation was induced in DEN-2- and JEV-infected cells. The mechanism and consequence of SGs formation during DEN-2 and JEV infection are of interest to be further studied.
"Design and Evaluation of a Non-Structural Protein 1-Based Diagnostic Zika Virus Infection." Tulane University, 2020.
Знайти повний текст джерелаZika 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.
1
Brandon Beddingfield
"Vaccination Strategy To Protect Against Flavivirus Infection Based On Recombinant Measles Vaccine." Doctoral diss., 2016. http://hdl.handle.net/2286/R.I.40803.
Повний текст джерелаDissertation/Thesis
Doctoral Dissertation Microbiology 2016
Chiu, Wei-Tzu, and 邱唯慈. "To study the potential modulation effect of cellular microRNA on flavivirus infection." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/75479753331429099807.
Повний текст джерела國防醫學院
微生物及免疫學研究所
98
MicroRNAs (miRNAs) are small noncoding RNAs of approximately 21~23 nucleotides in length. They are derived from cellular or viral transcripts and bind to their target mRNAs in a sequence-specific manner, resulting in either mRNA degradation or translational repression. Recent studies suggest that cellular miRNAs are among the key determinants controlling virus infection in mammalian hosts, for example cellular miRNAs can serve as restriction factors to limit infection by several viruses, including human immunodeficiency virus and vesicular stomatitis virus. However, our understanding on the role played by cellular miRNA on flaviviruses is limited.
Regner, Matthias. "The cytotoxic T Cell response to flavivirus infection : immunodominance and cross-reactivities." Phd thesis, 2000. http://hdl.handle.net/1885/147169.
Повний текст джерелаLee, Chyan-Jang, and 李乾彰. "I. Flavivirus Activates Phosphatidylinositol 3-Kinase Signaling to Block Caspase-Dependent Apoptotic Cell Death at The Early Stage of Virus InfectionII. The Roles of Cholesterol on Flavivirus Infection." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/75558075014203945874.
Повний текст джерела國防醫學院
生命科學研究所
93
Flaviviruses such as dengue virus (DEN) and Japanese encephalitis virus (JEV) are medically important in humans. The lipid kinase, phosphatidylinositol 3-kinase (PI3K) and its downstream target Akt have been implicated in the regulation of diverse cellular functions such as proliferation, and apoptosis. As JEV and DEN appear to trigger apoptosis in cultured cells at a rather late stage of infection, we evaluated the possible roles of the PI3K/Akt signaling pathway in flavivirus-infected cells. We found that Akt phosphorylation was noticeable in the JEV- and DEN serotype 2 (DEN-2)-infected neuronal N18 cells in an early, transient, PI3K- and lipid raft-dependent manner. Blocking of PI3K activation by its specific inhibitor LY294002 or wortmannin greatly enhanced virus-induced cytopathic effects (CPEs), even at an early stage of infection, but had no effect on virus production. This severe CPE was characterized as apoptotic cell death as evidenced by TUNEL staining and cleavage of caspase-3 and poly(ADP-ribose) polymerase (PARP). Mechanically, the initiator and effector caspases involved are mainly caspase-9 and caspase-6, as only a pan-caspase inhibitor and the inhibitors preferentially target caspase-9 and -6, but not the ones antagonizing caspase-8, -3 or -7 alleviated the levels of PARP cleavage following virus infection and PI3K blockage. Furthermore, Bcl-2 appears to be a crucial mediator downstream of PI3K/Akt signaling, as overexpression of Bcl-2 reduced virus-induced apoptosis even when PI3K activation was repressed. Collectively, our results suggest an antiapoptotic role for the PI3K/Akt pathway triggered by JEV and DEN-2 to protect infected cells from early apoptotic cell death. Japanese encephalitis virus (JEV) and dengue virus serotype 2 (DEN-2) are enveloped flaviviruses that enter cells via receptor-mediated endocytosis and low-pH-triggered membrane fusion, then replicate at intracellular membrane structures. Lipid rafts, the cholesterol-enriched lipid-ordered membrane domains, are platforms for a variety of cellular functions. In this study, we found that disruption of lipid raft formation by cholesterol depletion of chelating with methyl--cyclodextrin or filipin III reduced JEV and DEN-2 infections mainly at the intracellular replication steps, and to a lesser extent on viral entry. By membrane flotation assay, we further demonstrated that several flaviviral nonstructural proteins were associated with detergent-resistant membrane structures, indicating the replication complex of JEV and DEN-2 are localized at the membranes possessing lipid raft property. Interestingly, we also found that extra amount of cholesterol readily blocked flaviviral infection, in great contrast to an alphavirus, sindbis virus whose infection was enhanced by cholesterol. Cholesterol might reduce the levels of viral RNA uncoating, but not at the initial infection steps of viral binding and entry. The anti-flaviviral effects of cholesterol might also take place intracellularly in the steps post viral adsorption. Our results thus suggest a stringent requirement of membrane components, especially the amounts of cholesterol for various steps of flavivirus life cycle.
Pan, Hsuan-Fan, and 潘璿帆. "Study of inhibitory effects of flavivirus infection by the extracts of the Ulva lactuca." Thesis, 2007. http://ndltd.ncl.edu.tw/handle/01969503975163751629.
Повний текст джерела國立臺灣海洋大學
食品科學系
95
Viral infectious diseases caused by arthropod-borne flaviviruses have been gradually increased worldwide in recent years, especially including dengue virus (DEN) and Japanese encephalitis virus (JEV) prevalent in Taiwan and other South Asia countries. Dengue viruses cause dengue fever and dengue related diseases that represent a global public health problem. Seaweeds have known to possess an ingredient of sulfated polysaccharides that have been widely used as curative agents for anti-virus, anti-tumor, anti-oxidation, anti-coagulant, and control of normal cholesterol levels. The main purpose of this thesis is to study, by using cell cultures, the anti-DEN effect of the water-soluble extracts from Ulva lactuca, which belongs to green seaweed. Three homogeneous extracts of Ulva lactuca leaves, A1, A4 and A8, were used in this study and we found them had no cytotoxicity to the cultured cells at as high as 100 µg/ml. By indirect immunofluorescence assay, we observed that 100 µg/ml of A4 or A8 could suppress DEN infection to BHK-21 cells by 90%, and similarly we found they could also inhibit DEN infection to human hepatocyte HepG2 cells. We further noticed that these extracts were active against DEN infection only during the early stage of virus adsorption and penetration. Moreover, another flavivirus JEV was also found to be blocked to certain degrees by Ulva lactuca extracts when infected to BHK-21 cells. However, Sindbis virus, a member of Alphaviruses, appeared to be not suppressed by these extracts even their concentrations were used as high as 500 µg/ml. Together, our results demonstrate that the extracts from green seaweed Ulva lactuca, comprising abundant sulfated polysaccharides, have a specific anti-flavivirus effect in cultured system and the medical values of these extracts are worth further studying.