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Related Experiment Videos

HLA-Cw*04 and hepatitis C virus persistence.

Chloe L Thio1, Xiaojiang Gao, James J Goedert

  • 1Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, USA. cthio@jhmi.edu

Journal of Virology
|April 23, 2002
PubMed
Summary

Human leukocyte antigen (HLA) genes significantly influence hepatitis C virus (HCV) infection outcomes. Specific HLA alleles are associated with viral clearance, while others correlate with persistent HCV infection, suggesting a role in immune response.

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Area of Science:

  • Immunogenetics
  • Virology
  • Hepatology

Background:

  • The early host immune response is critical in determining the outcome of acute hepatitis C virus (HCV) infection, influencing viral persistence.
  • Class I human leukocyte antigens (HLA) are key components of the immune response, presenting foreign antigens to cytolytic T cells.
  • The high polymorphism of HLA genes suggests they may play a significant role in the varying outcomes of HCV infections.

Purpose of the Study:

  • To investigate the hypothesis that highly polymorphic HLA genes impact the outcome of HCV infection, specifically viral clearance versus persistence.
  • To identify specific HLA alleles associated with spontaneous clearance of HCV infection.
  • To identify specific HLA alleles associated with chronic HCV infection.

Main Methods:

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  • Molecular typing of HLA genes was performed on 231 individuals with documented HCV clearance and 444 matched individuals with persistent HCV infection.
  • Statistical analysis, including odds ratios (OR) and 95% confidence intervals (95% CI), was used to assess the association between HLA alleles and infection outcomes.
  • Linkage disequilibrium analysis was conducted to explore associations between linked HLA alleles and haplotypes.

Main Results:

  • Specific HLA alleles, including HLA-A*1101, HLA-B*57, and HLA-Cw*0102, were significantly associated with viral clearance (e.g., HLA-A*1101 OR=0.49).
  • Conversely, HLA-A*2301 and HLA-Cw*04 were associated with viral persistence (e.g., HLA-A*2301 OR=1.78).
  • HLA-Cw*04 showed a codominant association with persistence and may involve natural killer cells due to its interaction with killer immunoglobulin-like receptors.

Conclusions:

  • Specific class I HLA alleles are demonstrably associated with either the clearance or persistence of HCV infection.
  • The findings highlight the critical role of host genetic factors, particularly HLA polymorphisms, in controlling HCV infection.
  • Further research is warranted to elucidate the precise mechanisms by which HLA class I alleles influence HCV clearance and persistence.