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Journal of Virology, January 2007, p. 441-445, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01897-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Genetic Protection against Hepatitis B Virus Conferred by CCR5{Delta}32: Evidence that CCR5 Contributes to Viral Persistence{triangledown}

Chloe L. Thio,1 Jacquie Astemborski,1 Arman Bashirova,1 Timothy Mosbruger,1 Spencer Greer,1 Mallory D. Witt,2 James J. Goedert,3 Margaret Hilgartner,4 Audrey Majeske,1 Stephen J. O'Brien,5 David L. Thomas,1 and Mary Carrington5*

Department of Medicine, Johns Hopkins University, Baltimore, Maryland,1 Los Angeles Biomedical Research Institute at Harbor-UCLA and the David Geffen School of Medicine at UCLA,2 Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland,3 Department of Pediatrics, New York Presbyterian Hospital-Cornell Medical Center, New York, New York,4 Laboratory of Genomic Diversity, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland5

Received 31 August 2006/ Accepted 21 October 2006

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 (CCR5{Delta}32 [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 CCR5{Delta}32 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. CCR5{Delta}32 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 CCR5{Delta}32 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.

* Corresponding author. Mailing address: P.O. Box B, Laboratory of Genomic Diversity, NCI-Frederick, Frederick, MD 21702. Phone: (301) 846-1390. Fax: (301) 846-6771. E-mail: carringt{at}ncifcrf.gov.

{triangledown} Published ahead of print on 1 November 2006.

Journal of Virology, January 2007, p. 441-445, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01897-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Thio, C. L., Astemborski, J., Thomas, R., Mosbruger, T., Witt, M. D., Goedert, J. J., Hoots, K., Winkler, C., Thomas, D. L., Carrington, M. (2008). Interaction between RANTES Promoter Variant and CCR5{Delta}32 Favors Recovery from Hepatitis B. J. Immunol. 181: 7944-7947 [Abstract] [Full Text]  


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