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Journal of Virology, November 2000, p. 10752-10765, Vol. 74, No. 22
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Testing the Hypothesis of a Recombinant Origin of Human Immunodeficiency Virus Type 1 Subtype E

Jon P. Anderson,1,* Allen G. Rodrigo,2,dagger Gerald H. Learn,2 Anup Madan,1 Claire Delahunty,1 Michael Coon,2 Marc Girard,3 Saladin Osmanov,4 Leroy Hood,1 and James I. Mullins2

Departments of Molecular Biotechnology1 and Microbiology,2 Health Sciences Center, University of Washington, Seattle, Washington 98195; Virologie Moleculaire, Institut Pasteur, 75724 Paris Cedex 15, France3; and Joint United Nations Programme on HIV/AIDS (UNAIDS), Geneva CH-1211, Switzerland4

Received 10 December 1999/Accepted 4 August 2000

The human immunodeficiency virus type 1 (HIV-1) epidemic in Southeast Asia has been largely due to the emergence of clade E (HIV-1E). It has been suggested that HIV-1E is derived from a recombinant lineage of subtype A (HIV-1A) and subtype E, with multiple breakpoints along the E genome. We obtained complete genome sequences of clade E viruses from Thailand (93TH057 and 93TH065) and from the Central African Republic (90CF11697 and 90CF4071), increasing the total number of HIV-1E complete genome sequences available to seven. Phylogenetic analysis of complete genomes showed that subtypes A and E are themselves monophyletic, although together they also form a larger monophyletic group. The apparent phylogenetic incongruence at different regions of the genome that was previously taken as evidence of recombination is shown to be not statistically significant. Furthermore, simulations indicate that bootscanning and pairwise distance results, previously used as evidence for recombination, can be misleading, particularly when there are differences in substitution or evolutionary rates across the genomes of different subtypes. Taken jointly, our analyses suggest that there is inadequate support for the hypothesis that subtype E variants are derived from a recombinant lineage. In contrast, many other HIV strains claimed to have a recombinant origin, including viruses for which only a single parental strain was employed for analysis, do indeed satisfy the statistical criteria we propose. Thus, while intersubtype recombinant HIV strains are indeed circulating, the criteria for assigning a recombinant origin to viral structures should include statistical testing of alternative hypotheses to avoid inappropriate assignments that would obscure the true evolutionary properties of these viruses.

* Corresponding author. Mailing address: University of Washington, Box 357705, Seattle, WA 98195-7705. Phone: (206) 543-0557. Fax: (206) 543-3967. E-mail: jonand{at}u.washington.edu.

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

Journal of Virology, November 2000, p. 10752-10765, Vol. 74, No. 22
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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