Biology Faculty Articles

Document Type

Article

Publication Date

1-15-2007

Publication Title

Journal of Virology

ISSN

0022-538X

Volume

81

Issue/No.

2

First Page

441

Last Page

445

Abstract

Recovery from acute hepatitis B virus (HBV) infection requires a broad, vigorous T-cell response, which is enhanced in mice when chemokine receptor 5 (CCR5) is missing. To test the hypothesis that production of a nonfunctional CCR5 (CCR5Δ32 [a functionally null allele containing a 32-bp deletion]) increases the likelihood of recovery from hepatitis B in humans, we studied 526 persons from three cohorts in which one person with HBV persistence was matched to two persons who recovered from an HBV infection. Recovery or persistence was determined prior to availability of lamivudine. We determined genotypes forCCR5Δ32 and for polymorphisms in the CCR5 promoter and in coding regions of the neighboring genes, chemokine receptor 2 (CCR2) and chemokine receptor-like 2 (CCRL2). Allele and haplotype frequencies were compared among the 190 persons with viral recovery and the 336 with persistence by use of conditional logistic regression. CCR5Δ32 reduced the risk of developing a persistent HBV infection by nearly half (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33 to 0.83; P = 0.006). This association was virtually identical in persons with and without a concomitant human immunodeficiency virus infection. Of the nine individuals who were homozygous for the deletion, eight recovered from infection (OR, 0.25; 95% CI, 0.03 to 1.99; P = 0.19). None of the other neighboring polymorphisms examined were associated with HBV outcome. These data demonstrate a protective effect of CCR5Δ32 in recovery from an HBV infection, provide genetic epidemiological evidence for a role of CCR5 in the immune response to HBV, and suggest a potential therapeutic treatment for patients persistently infected with HBV.

Comments

© 2007, American Society for Microbiology

Additional Comments

NIH grant #s: DA00441, UO1-AI-35042, 5-MO1-_x000D_ RR-00722 [GCRC], UO1-AI-35043, UO1-AI-37984, UO1-AI-35039,_x000D_ UO1-AI-35040, UO1-AI-37613, UO1-AI-35041, MO1-RR06020, MO1-RR00071, MO1-RR00059, MO1-RR02558, R01-HD-4-1224, NO1-CO-12400; NCI contract #: N01-CP-33002; Bureau of Maternal and Child Health and Resources Development contract #: MCJ-060570; National Institute of Child Health and Human Development contract #: NO1-HD-4-3200

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

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