HLA-Cw*04 and hepatitis C virus persistence - PubMed (original) (raw)

Comparative Study

HLA-Cw*04 and hepatitis C virus persistence

Chloe L Thio et al. J Virol. 2002 May.

Abstract

In studies of acute hepatitis C virus (HCV) infection, the early host immune response is one of the determinants of viral persistence. The class I human leukocyte antigens (HLA), which present foreign antigen to cytolytic T cells, are integral components of this response. We hypothesized that the highly polymorphic HLA genes affect the outcome of an HCV infection. To test this hypothesis, we molecularly typed 231 persons with well-documented clearance of an HCV infection and 444 matched persistently infected persons. HLA-A*1101 (odds ratio [OR], 0.49; 95% confidence interval [95% CI], 0.27 to 0.89), HLA-B*57 (OR, 0.62; 95% CI, 0.39 to 1.00), and HLA-Cw*0102 (OR, 0.43; 95% CI, 0.21 to 0.89) were associated with viral clearance, whereas HLA-A*2301 (OR, 1.78; 95% CI, 1.01 to 3.11) and HLA-Cw*04 (OR, 1.78; 95% CI, 1.21 to 2.59) were associated with viral persistence. HLA-Cw*04 is in strong linkage disequilibrium with HLA-B*53 and HLA-B*35, but only HLA-B*53 (OR, 1.70; 95% CI, 0.95 to 3.06) and the Cw*04-B*53 haplotype (OR, 1.76; 95% CI, 0.94 to 3.26) were weakly associated with viral persistence. HLA-B*53 has similar, but not necessarily identical, binding specificity to some HLA-B*35 subtypes (B*35-Px group). The association with the B*35-Px group was less strong than with HLA-B*53 alone. The association of HLA-Cw*04 with HCV persistence was codominant (two copies of the gene were more strongly associated with persistence than one copy). However, HLA-Cw*04 was not associated with HCV RNA levels among the persistently infected individuals. Since Cw*04 is a ligand for the killer immunoglobulin-like receptors on natural killer cells, these cells may be involved in recovery from HCV infection. Further investigation is needed to understand the relationship between class I alleles and HCV clearance.

PubMed Disclaimer

Similar articles

Cited by

References

    1. Anonymous. 1997. National Institutes of Health Consensus Development Conference Panel statement: management of hepatitis C. Hepatology 26:2S-10S. - PubMed
    1. Barber, L. D., B. Gillece-Castro, L. Percival, X. Li, C. Clayberger, and P. Parham. 1995. Overlap in the repertoires of peptides bound in vivo by a group of related class I HLA-B allotypes. Curr. Biol. 5:179-190. - PubMed
    1. Barrett, S., E. Ryan, and J. Crowe. 1999. Association of the HLA-DRB1*01 allele with spontaneous viral clearance in an Irish cohort infected with hepatitis C virus via contaminated anti-D immunoglobulin. J. Hepatol. 30:979-983. - PubMed
    1. Carrington, M., G. W. Nelson, M. P. Martin, T. Kissner, D. Vlahov, J. J. Goedert, R. Kaslow, S. Buchbinder, K. Hoots, and S. J. O'Brien. 1999. HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science 283:1748-1752. - PubMed
    1. Cohen, G. B., R. T. Gandhi, D. M. Davis, O. Mandelboim, B. K. Chen, J. L. Strominger, and D. Baltimore. 1999. The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells. Immunity 10:661-671. - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources