HLA-Cw*04 and hepatitis C virus persistence

Chloe L Thio, Xiaojiang Gao, James J. Goedert, David Vlahov, Kenrad Edwin Nelson, Margaret W. Hilgartner, Stephen J. O'Brien, Peter Karacki, Jacquie Astemborski, Mary Carrington, David L Thomas

Research output: Contribution to journalArticle

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-A1101 (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.

Original languageEnglish (US)
Pages (from-to)4792-4797
Number of pages6
JournalJournal of Virology
Volume76
Issue number10
DOIs
StatePublished - 2002

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Hepatitis C virus
HLA Antigens
Hepacivirus
odds ratio
confidence interval
Odds Ratio
Confidence Intervals
Virus Diseases
HLA antigens
infection
KIR Receptors
Linkage Disequilibrium
natural killer cells
Cellular Structures
linkage disequilibrium
Natural Killer Cells

ASJC Scopus subject areas

  • Immunology

Cite this

HLA-Cw*04 and hepatitis C virus persistence. / Thio, Chloe L; Gao, Xiaojiang; Goedert, James J.; Vlahov, David; Nelson, Kenrad Edwin; Hilgartner, Margaret W.; O'Brien, Stephen J.; Karacki, Peter; Astemborski, Jacquie; Carrington, Mary; Thomas, David L.

In: Journal of Virology, Vol. 76, No. 10, 2002, p. 4792-4797.

Research output: Contribution to journalArticle

Thio, CL, Gao, X, Goedert, JJ, Vlahov, D, Nelson, KE, Hilgartner, MW, O'Brien, SJ, Karacki, P, Astemborski, J, Carrington, M & Thomas, DL 2002, 'HLA-Cw*04 and hepatitis C virus persistence', Journal of Virology, vol. 76, no. 10, pp. 4792-4797. https://doi.org/10.1128/JVI.76.10.4792-4797.2002
Thio, Chloe L ; Gao, Xiaojiang ; Goedert, James J. ; Vlahov, David ; Nelson, Kenrad Edwin ; Hilgartner, Margaret W. ; O'Brien, Stephen J. ; Karacki, Peter ; Astemborski, Jacquie ; Carrington, Mary ; Thomas, David L. / HLA-Cw*04 and hepatitis C virus persistence. In: Journal of Virology. 2002 ; Vol. 76, No. 10. pp. 4792-4797.
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AU - Thio, Chloe L

AU - Gao, Xiaojiang

AU - Goedert, James J.

AU - Vlahov, David

AU - Nelson, Kenrad Edwin

AU - Hilgartner, Margaret W.

AU - O'Brien, Stephen J.

AU - Karacki, Peter

AU - Astemborski, Jacquie

AU - Carrington, Mary

AU - Thomas, David L

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N2 - 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-A1101 (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.

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