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Blood, 1 September 2007, Vol. 110, No. 5, pp. 1559-1569. Prepublished online as a Blood First Edition Paper on May 2, 2007; DOI 10.1182/blood-2007-01-069583. This Article Full Text (PDF) All Versions of this Article: blood-2007-01-069583v1 110/5/1559    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Schulze zur Wiesch, J. Articles by Walker, B. D Search for Related Content PubMed PubMed Citation Articles by Schulze zur Wiesch, J. Articles by Walker, B. D Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 29, 2007 Accepted March 23, 2007 Immunologic evidence for lack of heterologous protection following resolution of HCV in subjects with non-genotype 1 infection Julian Schulze zur Wiesch*, Georg M Lauer, Joerg Timm, Thomas Kuntzen, Martin Neukamm, Andrew Berical, Andrea M Jones, Brian E Nolan, Steve A Longworth, Victoria Kasprowicz, Cory McMahon, Alysse Wurcel, Ansgar W Lohse, Lia L Lewis-Ximenez, Raymond T. Chung, Arthur Y Kim, Todd M Allen, and Bruce D Walker Heinrich Pette Institute for Experimental Virology, Hamburg, Germany Partners Aids Research Center, Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States Institute for Virology, University of Essen, Essen, Germany Medizinische Klinik I, Universitaetsklinikum Eppendorf, Hamburg, Germany Departmento de Virologia, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Brazil Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States Howard Hughes Medical Institute, Chevy Chase, MD, United States * Corresponding author; email: julianszw{at}gmail.com. Chronic HCV infection is typically characterized by a lack of virus-specific CD4+ T-cell proliferative responses, but strong responses have been described in a subset of persons with persistent viremia. One possible explanation for these responses is that they were primed by an earlier resolved infection and do not recognize the current circulating virus. We defined all targeted epitopes utilizing overlapping peptides corresponding to a genotype 1a strain in 44 subjects chronically infected with different HCV genotypes (GT). Surprisingly, more HCV-specific CD4+ T cell responses were detected in subjects with chronic non-GT1 infection compared to subjects with chronic GT1 infection (p=0.017). Notably, we found serological evidence of a previous exposure to GT1 in four subjects with non-GT1 infection, and these persons also demonstrated significantly more responses than non-GT1 subjects in whom genotype and HCV serotype were identical (p=0.0003). Comparison of recognition of GT1-specific peptides to peptides representing autologous virus revealed the absence of cross-recognition of the autologous circulating virus. These data indicate that persisent HCV infection can occur in the presence of an HCV-specific T-cell response primed against a heterologous HCV strain, and suggest that clearance of one GT does not necessarily protect against subsequent exposure to a second GT. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: CD4+ T cells don't always help Christoph Neumann-Haefelin and Robert Thimme Blood 2007 110: 1408-1409. [Full Text] [PDF]

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