Analysis of diversity of hepatitis C virus glycoproteins E1 and E2

作者: Natalia Joanna Hudson

DOI:

关键词: VirologyWindow periodInfectivityHorizontal transmissionSeroconversionBiologyHepatitis C virusPopulationSelective sweepHypervariable region

摘要: Hepatitis C Virus (HCV) exists as a population of sequence variants that evolves during infection adapting to host pressures. The main targets for the immune response are envelope glycoproteins E1 and E2, which also mediate viral cell entry. first hypervariable region (HVR1) previously implicated in outcome acute infection, has been focus many studies. However more broadly neutralising antibodies tend target epitopes outside this region, yet evolution full length E1E2 heterodimer is poorly understood. HCV transmission window period well seroconversion evolutionary events shaping primary hence influencing infection. However, due asymptomatic character early phases data describing interval still lacking depth. Defining genetic phenotypic characteristics establish new would aid vaccine therapy design. This study aimed identify patterns glycoprotein upon disease. We studied three settings: experimental immunocompromised mice by known inoculum; occurrence horizontal haemodialysis unit between hypothesised source index case individuals; unrelated cases acutely infected patients. single genome amplification (SGA) approach was utilised, allowed us accurately assign linkage substitutions determine frequency distribution analysed populations. Data from setting indicates selective sweep occurs transmission, with possess fitness advantage at entry level. Molecular determinants associated enhanced infectivity have identified. In further part project we confirmed use phylogenetic methods suggested revision current safety guidelines. Analysis sequences last showed indeed HVR1 might not be good enough indicator phase, linked occur region. Seroconversion increasing diversity indicating role driving evolution, specific.

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