JVI Accepts, published online ahead of print on 6 June 2007

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J. Virol. doi:10.1128/JVI.00463-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Recombination is confounding the early evolutionary history of HIV-1: subtype G is a circulating recombinant form

Ana B Abecasis, Philippe Lemey, Nicole Vidal, Túlio de Oliveira, Martine Peeters, Ricardo Camacho, Beth Shapiro, Andrew Rambaut, and Anne-Mieke Vandamme^*

Laboratory for Clinical and Epidemiological Virology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium; Laboratório de Virologia, Serviço de Imunohemoterapia, Hospital de Egas Moniz., Rua da Junqueira, 126, 1349-019 Lisbon, Portugal; Evolutionary Biology Group, Department of Zoology, University of Oxford., South Parks Road, Oxford OX1 3PS, U.K.; Laboratory Retrovirus, IRD, IRD - UMR 145, 911, Av. Agropolis - BP 64501, 34394 Montpellier Cedex 5, France

^* To whom correspondence should be addressed. Email: annemie.vandamme{at}uz.kuleuven.be.

HIV-1 is classified in 9 subtypes (A-D, F, G, H, J and K), sub-subtypes and several Circulating Recombinant Forms (CRFs). Due to the high level of genetic diversity within HIV-1 and to its worldwide distribution, this classification system is widely used in fields as diverse as vaccine development, evolution, epidemiology, viral fitness and drug resistance. Here, we demonstrate how the high recombination rates of HIV-1 may confound the study of its evolutionary history and classification. Our data show that subtype G, currently classified as pure subtype, has in fact a recombinant history, having evolved following recombination between subtypes A, J and a putative subtype G parent. In addition, we find no evidence for recombination within one of the lineages currently classified as a CRF, CRF02_AG. Our analysis indicates that "CRF02_AG" was the parent of the recombinant "subtype G," rather than having the opposite evolutionary relationship as is currently proposed.

Our results imply that the current classification of HIV-1 subtypes and CRFs is an artifact of sampling history, rather than reflecting the evolutionary history of the virus. We suggest a re-analysis of all pure subtypes and CRFs in order to better understand how high rates of recombination have influenced HIV-1 evolutionary history.

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