Transmitted/Founder Viruses Rapidly Escape from CD8+ T Cell Responses in Acute Hepatitis C Virus Infection

Journal of Virology
Rowena A BullFabio Luciani

Abstract

The interaction between hepatitis C virus (HCV) and cellular immune responses during very early infection is critical for disease outcome. To date, the impact of antigen-specific cellular immune responses on the evolution of the viral population establishing infection and on potential escape has not been studied. Understanding these early host-virus dynamics is important for the development of a preventative vaccine. Three subjects who were followed longitudinally from the detection of viremia preseroconversion until disease outcome were analyzed. The evolution of transmitted/founder (T/F) viruses was undertaken using deep sequencing. CD8(+) T cell responses were measured via enzyme-linked immunosorbent spot (ELISpot) assay using HLA class I-restricted T/F epitopes. T/F viruses were rapidly extinguished in all subjects associated with either viral clearance (n = 1) or replacement with viral variants leading to establishment of chronic infection (n = 2). CD8(+) T cell responses against 11 T/F epitopes were detectable by 33 to 44 days postinfection, and 5 of these epitopes had not previously been reported. These responses declined rapidly in those who became chronically infected and were maintained in the subject who cleared infe...Continue Reading

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Feb 11, 2016·Immunology and Cell Biology·Auda A EltahlaFabio Luciani
Nov 26, 2015·Gastroenterology Clinics of North America·David E Kaplan
Aug 26, 2016·Journal of Viral Hepatitis·E KeoshkerianUNKNOWN HITS-p and HITS-c investigators
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Mar 25, 2020·Cold Spring Harbor Perspectives in Medicine·Stephanie SmithChristopher Walker

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