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

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 (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.

SUBMITTER: Thio CL

PROVIDER: S-EPMC1797425 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature

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

Thio Chloe L CL Astemborski Jacquie J Bashirova Arman A Mosbruger Timothy T Greer Spencer S Witt Mallory D MD Goedert James J JJ Hilgartner Margaret M Majeske Audrey A O'Brien Stephen J SJ Thomas David L DL Carrington Mary M

Journal of virology 20061101 2

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 ...[more]

PMID: 17079285

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Project description:UnlabelledHepatitis E viral (HEV) infection imposes a heavy health burden worldwide and is common in the United States. Previous investigations of risks addressed environmental and host behavioral/lifestyle factors, but host genetic factors have not been examined. We assessed strength of associations between antibody to HEV (anti-HEV) immunoglobulin G seropositivity indicating past or recent HEV infection and human genetic variants among three major racial/ethnic populations in the United States, involving 2434 non-Hispanic whites, 1919 non-Hispanic blacks, and 1919 Mexican Americans from the Third National Health and Nutrition Examination Survey, 1991-1994. We studied 497 single-nucleotide polymorphisms across 190 genes (particularly those associated with lipid metabolism). The genomic control method was used to adjust for potential population stratification. Non-Hispanic blacks had the lowest seroprevalence of anti-HEV immunoglobulin G (15.3%, 95% confidence interval [CI] 12.3%-19.0%) compared with non-Hispanic whites (22.3%, 95% CI 19.1%-25.7%) and Mexican Americans (21.8%, 95% CI 19.0%-25.3%; P<0.01). Non-Hispanic blacks were the only population that showed association between anti-HEV seropositivity and functional ε3 and ε4 alleles of the apolipoprotein E (APOE) gene, encoding the apolipoprotein E protein that mediates lipoprotein metabolism. Seropositivity was significantly lower in participants carrying APOE ε4 (odds ratio=0.5, 95% CI 0.4-0.7; P=0.00004) and ε3 (odds ratio=0.6, 95% CI 0.4-0.8; P=0.001) compared to those carrying APOE ε2. No significant associations were observed between other single-nucleotide polymorphisms and anti-HEV seropositivity in non-Hispanic blacks or between any single-nucleotide polymorphisms and anti-HEV seropositivity in non-Hispanic whites or Mexican Americans.ConclusionBoth APOE ε3 and ε4 are significantly associated with protection against HEV infection in non-Hispanic blacks; additional studies are needed to understand the basis of protection so that preventive services can be targeted to at-risk persons.

Dataset Information

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

Publications

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

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