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Journal of Virology, May 2007, p. 4492-4500, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.02050-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Extensive Intrasubtype Recombination in South African Human Immunodeficiency Virus Type 1 Subtype C Infections{triangledown}

Christine M. Rousseau,1* Gerald H. Learn,1 Tanmoy Bhattacharya,2 David C. Nickle,1 David Heckerman,3 Senica Chetty,4 Christian Brander,5 Philip J. R. Goulder,5,6 Bruce D. Walker,5,7 Photini Kiepiela,4 Bette T. Korber,2 and James I. Mullins1

Department of Microbiology, University of Washington, Seattle, Washington 98195-8070,1 Los Alamos National Laboratory, Los Alamos, New Mexico 87545,2 Machine Learning and Applied Statistics Group, Microsoft Research, Redmond, Washington 98052,3 HIV Pathogenesis Program, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban 4015, South Africa,4 Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129,5 Nuffield Department of Medicine, The Peter Medawar Building for Pathogen Research, Oxford University, Oxford OX1 3SY, United Kingdom,6 Howard Hughes Medical Institute, Chevy Chase, Maryland 208157

Received 19 September 2006/ Accepted 14 February 2007

Recombinant human immunodeficiency virus type 1 (HIV-1) strains containing sequences from different viral genetic subtypes (intersubtype) and different lineages from within the same subtype (intrasubtype) have been observed. A consequence of recombination can be the distortion of the phylogenetic signal. Several intersubtype recombinants have been identified; however, less is known about the frequency of intrasubtype recombination. For this study, near-full-length HIV-1 subtype C genomes from 270 individuals were evaluated for the presence of intrasubtype recombination. A sliding window schema (window, 2 kb; step, 385 bp) was used to partition the aligned sequences. The Shimodaira-Hasegawa test detected significant topological incongruence in 99.6% of the comparisons of the maximum-likelihood trees generated from each sequence partition, a result that could be explained by recombination. Using RECOMBINE, we detected significant levels of recombination using five random subsets of the sequences. With a set of 23 topologically consistent sequences used as references, bootscanning followed by the interactive informative site test defined recombination breakpoints. Using two multiple-comparison correction methods, 47% of the sequences showed significant evidence of recombination in both analyses. Estimated evolutionary rates were revised from 0.51%/year (95% confidence interval [CI], 0.39 to 0.53%) with all sequences to 0.46%/year (95% CI, 0.38 to 0.48%) with the putative recombinants removed. The timing of the subtype C epidemic origin was revised from 1961 (95% CI, 1947 to 1962) with all sequences to 1958 (95% CI, 1949 to 1960) with the putative recombinants removed. Thus, intrasubtype recombinants are common within the subtype C epidemic and these impact analyses of HIV-1 evolution.

* Corresponding author. Mailing address: University of Washington, 1959 NE Pacific Street, Box 358070, Seattle, WA 98195-8070. Phone: (206) 732-6102. Fax: (206) 732-6167. E-mail: cmr{at}u.washington.edu

{triangledown} Published ahead of print on 21 February 2007.

Journal of Virology, May 2007, p. 4492-4500, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.02050-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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