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Journal of Virology, March 2009, p. 2715-2727, Vol. 83, No. 6
0022-538X/09/$08.00+0     doi:10.1128/JVI.01960-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Population Genetics and Adaptation in Newly Infected Individuals{triangledown} ,{dagger}

M. Kearney,1,2* F. Maldarelli,1 W. Shao,3 J. B. Margolick,4 E. S. Daar,5 J. W. Mellors,6 V. Rao,2 J. M. Coffin,7 and S. Palmer1,{ddagger}

HIV Drug Resistance Program, National Cancer Institute, National Institutes of Health, Frederick, Maryland,1 Department of Biology, Catholic University of America, Washington, D.C.,2 Advanced Biomedical Computing Center, SAIC, Frederick, Maryland,3 Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland,4 Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California,5 Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania,6 Department of Molecular Biology and Microbiology, Tufts University, Boston, Massachusetts7

Received 17 September 2008/ Accepted 22 December 2008

Studies on human immunodeficiency virus type 1 (HIV-1) diversity are critical for understanding viral pathogenesis and the emergence of immune escape variants and for design of vaccine strategies. To investigate HIV-1 population genetics, we used single-genome sequencing to obtain pro-pol and env sequences from longitudinal samples (n = 93) from 14 acutely or recently infected patients. The first available sample after infection for 12/14 patients revealed HIV-1 populations with low genetic diversity, consistent with transmission or outgrowth of a single variant. In contrast, two patients showed high diversity and coexistence of distinct virus populations in samples collected days after a nonreactive enzyme-linked immunosorbent assay or indeterminate Western blot, consistent with transmission or outgrowth of multiple variants. Comparison of PR and RT sequences from the first sample for all patients with the consensus subgroup B sequence revealed that nearly all nonsynonymous differences were confined to identified cytotoxic T-lymphocyte (CTL) epitopes. For HLA-typed patients, mutations compared to the consensus in transmitted variants were found in epitopes that would not be recognized by the patient's major histocompatibility complex type. Reversion of transmitted mutations was rarely seen over the study interval (up to 5 years). These data indicate that acute subtype B HIV-1 infection usually results from transmission or outgrowth of single viral variants carrying mutations in CTL epitopes that were selected prior to transmission either in the donor or in a previous donor and that reversion of these mutations can be very slow. These results have important implications for vaccine strategies because they imply that some HLA alleles could be compromised in newly acquired HIV infections.

* Corresponding author. Mailing address: HIV Drug Resistance Program, National Cancer Institute at Frederick, 1050 Boyles Street, Building 535, Room 109, Frederick, MD 21702-1201. Phone: (301) 846-6796. Fax: (301) 846-6013. E-mail: kearneym{at}ncifcrf.gov

{triangledown} Published ahead of print on 30 December 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} Present address: Swedish Institute for Infectious Disease Control, Karolinska Institute, Stockholm, Sweden.

Journal of Virology, March 2009, p. 2715-2727, Vol. 83, No. 6
0022-538X/09/$08.00+0     doi:10.1128/JVI.01960-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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