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Journal of Virology, May 2002, p. 4792-4797, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.4792-4797.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

HLA-Cw*04 and Hepatitis C Virus Persistence

Chloe L. Thio,1* Xiaojiang Gao,2 James J. Goedert,3 David Vlahov,4,5 Kenrad E. Nelson,4 Margaret W. Hilgartner,6 Stephen J. O'Brien,2 Peter Karacki,1 Jacquie Astemborski,1 Mary Carrington,2 and David L. Thomas1,4

Department of Medicine,1 Department of Epidemiology, Johns Hopkins Medical Institutions, Baltimore,4 Laboratory of Genomic Diversity, National Cancer Institute, Frederick,2 Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland,3 New York Academy of Medicine,5 Department of Pediatrics, New York Presbyterian Hospital-Cornell Medical Center, New York, New York6

Received 4 September 2001/ Accepted 15 February 2002

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.

* Corresponding author. Mailing address: Department of Medicine, Johns Hopkins University, 424 N. Bond St., Baltimore, MD 21231-1001. Phone: (410) 955-0349. Fax: (410) 614-7564. E-mail: cthio{at}jhmi.edu.

Journal of Virology, May 2002, p. 4792-4797, Vol. 76, No. 10
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.10.4792-4797.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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