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Journal of Virology, November 2002, p. 10674-10684, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.10674-10684.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Selection for Human Immunodeficiency Virus Type 1 Recombinants in a Patient with Rapid Progression to AIDS

Shan-Lu Liu,1,{dagger} John E. Mittler,1 David C. Nickle,1 Thera M. Mulvania,1,2 Daniel Shriner,1 Allen G. Rodrigo,1,3 Barry Kosloff,2 Xi He,1 Lawrence Corey,1,2,3,4 and James I. Mullins1,2,3*

Departments of Microbiology,1 Laboratory Medicine,2 Medicine, University of Washington, Seattle, Washington 98195,3 Fred Hutchinson Cancer Research Center, Seattle, Washington 981094

Received 7 March 2002/ Accepted 26 July 2002

Although human immunodeficiency virus type 1 (HIV-1) recombinants have been found with high frequency, little is known about the forces that select for these viruses or their importance to pathogenesis. Here we document the emergence and dynamics of 11 distinct HIV-1 recombinants in a man who was infected with two subtype B HIV-1 strains and progressed rapidly to AIDS without developing substantial cellular or humoral immune responses. Although numerous frequency oscillations were observed, a single recombinant lineage eventually came to dominate the population. Numerical simulations indicate that the successive recombinant forms displaced each other too rapidly to be explained by any simple model of random genetic drift or sampling variation. All of the recombinants, including several resulting from independent recombination events, possessed the same sequence motif in the V3 loop, suggesting intense selection on this segment of the viral envelope protein. The outgrowth of the predominant V3 loop recombinants was not, however, associated with changes in coreceptor utilization. The final variant was instead notable for having lost 3 of 14 potential glycosylation sites. We also observed high ratios of synonymous-to-nonsynonymous nucleotide changes—suggestive of purifying selection—in all viral populations, with particularly high ratios in newly arising recombinants. Our study, therefore, illustrates the unusual and important patterns of viral adaptation that can occur in a patient with weak immune responses. Although it is hard to tease apart cause and effect in a single patient, the correlation with disease progression in this patient suggests that recombination between divergent viruses, with its ability to create chimeras with increased fitness, can accelerate progression to AIDS.

* Corresponding author. Mailing address: Department of Microbiology, University of Washington, Seattle, WA 98195. Phone: (206) 616-1851. Fax: (360) 838-9259. E-mail: jmullins{at}u.washington.edu.

{dagger} Present addresses: Department of Pathology, University of Washington, Seattle, WA 98195, and Fred Hutchinson Cancer Research Center, Seattle, WA 98119.

{ddagger} Present address: Washington Regional Primate Research Center, Seattle, WA 98195.

§ Present address: School of Biological Sciences, University of Auckland, Auckland, New Zealand.

Journal of Virology, November 2002, p. 10674-10684, Vol. 76, No. 21
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.21.10674-10684.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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