Genetic protection against hepatitis B virus conferred by CCR5Delta32

2002落叶

J Virol. 2007 Jan;81(2):441-5. Epub 2006 Nov 1.

Genetic protection against hepatitis B virus conferred by CCR5Delta32:
Evidence that CCR5 contributes to viral persistence.

Thio CL, Astemborski J, Bashirova A, Mosbruger T, Greer S, Witt MD, Goedert
JJ, Hilgartner M, Majeske A, O'Brien SJ, Thomas DL, Carrington M.

Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

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 (CCR5Delta32 [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 for CCR5Delta32 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. CCR5Delta32 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 CCR5Delta32 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.