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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.
IMMUNOBIOLOGY Immunologic evidence for lack of heterologous protection following resolution of HCV in patients with non–genotype 1 infection
1 Partners AIDS Research Center, Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA;
2 Howard Hughes Medical Institute, Chevy Chase, MD;
3 Medizinische Klinik I, Universit Chronic hepatitis C virus (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 using overlapping peptides corresponding to a genotype 1a strain in 44 patients chronically infected with different HCV genotypes (GT). Surprisingly, more HCV-specific CD4+ T-cell responses were detected in patients with chronic non-GT1 infection compared with patients with chronic GT1 infection (P = .017). Notably, we found serologic evidence of a previous exposure to GT1 in 4 patients with non-GT1 infection, and these persons also demonstrated significantly more responses than non-GT1 patients in whom genotype and HCV serotype were identical (P < .001). 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 1 GT does not necessarily protect against subsequent exposure to a second GT.
Related Article in Blood Online:
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| Copyright © 2007 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
tsklinikum Eppendorf, Hamburg, Germany;
4 Heinrich Pette Institute for Experimental Virology, Hamburg, Germany;
5 University of Essen, Institute of Virology, Essen, Germany;
6 Departmento de Virologia, Instituto Oswaldo Cruz/Fiocruz, Rio de Janeiro, Brazil;
7 Gastrointestinal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA