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* Department of Medicine,
Department of Epidemiology, and
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL 35294;
Rwanda/Zambia HIV-1 Research Group, Lusaka, Zambia; and
¶ Department of Global Health and
|| Vaccine Research Center, Emory University, Atlanta, GA 30322
Differences in immune control of HIV-1 infection are often attributable to the highly variable HLA class I molecules that present viral epitopes to CTL. In our immunogenetic analyses of 429 HIV-1 discordant Zambian couples (infected index partners paired with cohabiting seronegative partners), several HLA class I variants in index partners were associated with contrasting rates and incidence of HIV-1 transmission within a 12-year study period. In particular, A*3601 on the A*36-Cw*04-B*53 haplotype was the most unfavorable marker of HIV-1 transmission by index partners, while Cw*1801 (primarily on the A*30-Cw*18-B*57 haplotype) was the most favorable, irrespective of the direction of transmission (male to female or female to male) and other commonly recognized cofactors of infection, including age and GUI. The same HLA markers were further associated with contrasting viral load levels in index partners, but they had no clear impact on HIV-1 acquisition by the seronegative partners. Thus, HLA class I gene products not only mediate HIV-1 pathogenesis and evolution but also influence heterosexual HIV-1 transmission.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by National Institute of Allergy and Infectious Diseases through grants AI40951 (to S.A.), AI41530 (to J. Michael Kilby), AI41951 (to R.A.K.), AI51173 (to J.T.), and AI64060 (to E.H.). J.T. is the recipient of an Independent Scientist Award (AI76123) from National Institute of Allergy and Infectious Diseases.
2 Address correspondence and reprint requests to Dr. Jianming Tang or Dr. Richard A. Kaslow, Program in Epidemiology of Infection and Immunity, Schools of Medicine and Public Health, University of Alabama at Birmingham, 1665 University Boulevard, Birmingham, AL 35294-0022. E-mail address: jtang{at}uab.edu or rkaslow{at}uab.edu
3 Current address: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Canada.
4 Abbreviations used in this paper: LD, linkage disequilibrium; EM, expectation-maximization; D’, relative LD; GUI, genital ulcer/inflammation; HIV+, HIV-1 seropositive (infected); HIV–, HIV-1 seronegative (uninfected); OR, odds ratio; RH, relative hazard; TPI, transmission pair index; NTI, non-TPI; CI, confidence interval; Freq, frequency; MTF, male-to-female; FTM, female-to-male; SC, seroconverter; ESN, exposed seronegative; FUT, follow-up time; HWE, Hardy-Weinberg equilibrium; Freq, frequency; MTCT, mother-to-child transmission; age
, age difference; PIP, paired index partner; NA, not applicable.
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  H. Crawford, W. Lumm, A. Leslie, M. Schaefer, D. Boeras, J. G. Prado, J. Tang, P. Farmer, T. Ndung'u, S. Lakhi, et al. Evolution of HLA-B*5703 HIV-1 escape mutations in HLA-B*5703-positive individuals and their transmission recipients J. Exp. Med., April 13, 2009; 206(4): 909 - 921. [Abstract] [Full Text] [PDF]
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