CD8 epitope escape and reversion in acute HCV infection

The Journal of Experimental Medicine
Joerg TimmTodd M Allen

Abstract

In the setting of acute hepatitis C virus (HCV) infection, robust HCV-specific CD8+ cytotoxic T lymphocyte (CTL) responses are associated with initial control of viremia. Despite these responses, 70-80% of individuals develop persistent infection. Although viral escape from CD8 responses has been illustrated in the chimpanzee model of HCV infection, the effect of CD8 selection pressure on viral evolution and containment in acute HCV infection in humans remains unclear. Here, we examined viral evolution in an immunodominant human histocompatibility leukocyte antigen (HLA)-B8-restricted NS3 epitope in subjects with acute HCV infection. Development of mutations within the epitope coincided with loss of strong ex vivo tetramer and interferon gamma enzyme-linked immunospot responses, and endogenous expression of variant NS3 sequences suggested that the selected mutations altered processing and presentation of the variant epitope. Analysis of NS3 sequences from 30 additional chronic HCV-infected subjects revealed a strong association between sequence variation within this region and expression of HLA-B8, supporting reproducible allele-specific selection pressures at the population level. Interestingly, transmission of an HLA-B8-assoc...Continue Reading

References

Dec 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·T AebischerH Hengartner
May 1, 1987·Annals of Emergency Medicine·R C Jorden
Oct 4, 1996·Science·J D AltmanM M Davis
Jan 1, 1997·Springer Seminars in Immunopathology·M J Koziel, B D Walker
May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·X S HeH B Greenberg
Sep 25, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J M ChristieW M Rosenberg
May 3, 2000·The Journal of Experimental Medicine·F LechnerB D Walker
Jun 6, 2000·The Journal of Experimental Medicine·G E PriceD Moskophidis
Jul 7, 2001·The New England Journal of Medicine·G M Lauer, B D Walker
Nov 21, 2001·The Journal of Experimental Medicine·R ThimmeF V Chisari
May 3, 2002·Clinical and Experimental Immunology·S WardP Klenerman
Aug 29, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Eleanor BarnesPaul Klenerman
Sep 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heiner WedemeyerBarbara Rehermann
Jun 18, 2003·The Journal of Experimental Medicine·Naglaa H ShoukryChristopher M Walker
Aug 12, 2003·Trends in Immunology·Vito Racanelli, Barbara Rehermann
Sep 17, 2003·The Journal of Clinical Investigation·Cheryl L DayKai W Wucherpfennig
Oct 25, 2003·Science·Arash GrakouiChristopher M Walker
Jan 17, 2004·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Mauro ZaccarelliAndrea Antinori
Feb 11, 2004·Nature Medicine·A J LeslieP J R Goulder
Feb 18, 2004·Nature Medicine·Thomas C FriedrichDavid I Watkins
Apr 7, 2004·The Journal of Experimental Medicine·Rika DraenertPhilip J R Goulder

❮ Previous
Next ❯

Citations

Aug 23, 2012·Archivum Immunologiae Et Therapiae Experimentalis·Erwin Daniel Brenndörfer, Matti Sällberg
Feb 28, 2007·Current Infectious Disease Reports·Marianne Mikkelsen, Jens Bukh
Jul 10, 2007·Current Infectious Disease Reports·Arthur Y Kim, Georg M Lauer
Jan 13, 2010·Immunologic Research·Kelly P Burke, Andrea L Cox
Oct 22, 2008·Expert Reviews in Molecular Medicine·Barbara Roe, William W Hall
May 13, 2009·Immunology and Cell Biology·Mandvi BharadwajJames McCluskey
Jun 12, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ola WeilandMatti Sällberg
Aug 19, 2005·Nature·David G Bowen, Christopher M Walker
Aug 24, 2005·Nature Immunology·Paul Klenerman, Ann Hill
Mar 2, 2005·Nature Reviews. Immunology·Barbara Rehermann, Michelina Nascimbeni
Aug 28, 2013·Proceedings of the National Academy of Sciences of the United States of America·Michael J FullerChristopher M Walker
Jun 9, 2005·The Journal of Experimental Medicine·Ian TesterHugo R Rosen
Jun 9, 2005·The Journal of Experimental Medicine·Andrea L CoxStuart C Ray
Jun 9, 2005·The Journal of Experimental Medicine·Stuart C RayDavid L Thomas
Jun 9, 2005·The Journal of Experimental Medicine·David G Bowen, Christopher M Walker
Mar 3, 2006·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Georg M Lauer, Arthur Y Kim
May 18, 2006·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Barbara H McGovernGeorg M Lauer
Oct 18, 2011·Current Opinion in HIV and AIDS·Donatella Ciuffreda, Arthur Y Kim
Aug 12, 2006·Proceedings. Biological Sciences·W YaoL M Wahl
Aug 19, 2007·Journal of Virology·Thomas KuntzenTodd M Allen
Apr 9, 2010·Journal of Virology·Gary P WangFrederic D Bushman
Jul 15, 2005·Journal of Virology·Stefan F Wieland, Francis V Chisari

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsy
Assay
FCS
PCR
Transfection

Software Mentioned

TreeStar
Sequencher
FlowJo
MacClade
CODEML
CELLQuest
MacVector
PAUP
PAUP *

Related Concepts

Related Feeds

CZI Human Cell Atlas Seed Network

The aim of the Human Cell Atlas (HCA) is to build reference maps of all human cells in order to enhance our understanding of health and disease. The Seed Networks for the HCA project aims to bring together collaborators with different areas of expertise in order to facilitate the development of the HCA. Find the latest research from members of the HCA Seed Networks here.