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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

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.

Published ahead of print on 21 February 2007.