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Hepatitis C virus (HCV)-specific immune responses of long-term injection drug users frequently exposed to HCV

Mizukoshi, Eishiro and Eisenbach, Christoph and Edlin, Brian R and Newton, Kimberly P and Raghuraman, Sukanya and Weiler-Normann, Christina and Tobler, Leslie H and Busch, Michael P and Carrington, Mary and McKeating, Jane A and O'Brien, Thomas R and Rehermann, Barbara (2008) Hepatitis C virus (HCV)-specific immune responses of long-term injection drug users frequently exposed to HCV. The Journal of infectious diseases, 198 (2). pp. 203-12. ISSN 0022-1899

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BACKGROUND: Injection drug users (IDUs) who successfully clear hepatitis C virus (HCV) have a reduced risk of developing chronic reinfection, despite their continuing exposure to the virus. To identify immunological correlates for this apparent protection, we studied HCV-specific immune responses in long-term IDUs (duration, >10 years). METHODS: HCV-specific T cell responses were assessed in proliferation, enzyme-linked immunospot (ELISPOT), interferon (IFN)-gamma secretion, and cytotoxicity assays, whereas HCV-specific antibodies were assessed in enzyme immunoassays (EIAs), chemiluminescent assays, and in vitro neutralization assays. RESULTS: HCV-specific T cell proliferation and IFN-gamma production were more common in nonviremic EIA-positive IDUs (16 [94%] of 17 IDUs) than in viremic EIA-positive IDUs (9 [45%] of 20 IDUs) (P= .003). They were also noted in 16 (62%) of 26 nonviremic EIA-negative IDUs. In contrast, 19 (90%) of 21 viremic IDUs displayed neutralizing antibodies (nAbs), compared with 9 (56%) of 16 nonviremic EIA-positive IDUs (P= .04) and 0 of 24 nonviremic EIA-negative IDUs. Nonviremic IDUs with nAbs were older (P= .0115) than those without nAbs, but these groups did not differ in terms of either injection drug use duration or HCV-specific T cell responses. CONCLUSION: The reduced risk of HCV persistence in IDUs previously recovered from HCV infection correlated with T cell responses, and prolonged antigenic stimulation appears to be required to maintain humoral responses.

Type of Work:Article
Date:2008 (Publication)
School/Faculty:Schools (1998 to 2008) > School of Medicine
Department:Immunity and Infection
Subjects:R Medicine (General)
QR355 Virology
QR180 Immunology
QR Microbiology
Institution:University of Birmingham
Copyright Holders:the Infectious Diseases Society of America
ID Code:475
Refereed:YES
Local Holdings:
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