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Journal of Virology, June 2002, p. 5435-5451, Vol. 76, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.11.5435-5451.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Subtype C Molecular Phylogeny: Consensus Sequence for an AIDS Vaccine Design?

V. Novitsky,1 U. R. Smith,2 P. Gilbert,3 M. F. McLane,1 P. Chigwedere,1 C. Williamson,4 T. Ndung'u,1 I. Klein,1 S. Y. Chang,1 T. Peter,5 I. Thior,5 B. T. Foley,2 S. Gaolekwe,6 N. Rybak,1 S. Gaseitsiwe,5 F. Vannberg,7 R. Marlink,1 T. H. Lee,1 and M. Essex1*

Harvard School of Public Health,1 Harvard Medical School, Boston, Massachusetts,7 Los Alamos National Laboratory, Los Alamos, New Mexico,2 University of Washington, Seattle, Washington,3 University of Cape Town, Cape Town, South Africa,4 Botswana-Harvard Partnership for HIV Research and Education,5 National Health Laboratory/National Blood Transfusion Center, Gaborone, Botswana6

Received 25 October 2001/ Accepted 13 February 2002

An evolving dominance of human immunodeficiency virus type 1 subtype C (HIV-1C) in the AIDS epidemic has been associated with a high prevalence of HIV-1C infection in the southern African countries and with an expanding epidemic in India and China. Understanding the molecular phylogeny and genetic diversity of HIV-1C viruses may be important for the design and evaluation of an HIV vaccine for ultimate use in the developing world. In this study we analyzed the phylogenetic relationships (i) between 73 nonrecombinant HIV-1C near-full-length genome sequences, including 51 isolates from Botswana; (ii) between HIV-1C consensus sequences that represent different geographic subsets; and (iii) between specific isolates and consensus sequences. Based on the phylogenetic analyses of 73 near-full-length genomes, 16 "lineages" (a term that is used hereafter for discussion purposes and does not imply taxonomic standing) were identified within HIV-1C. The lineages were supported by high bootstrap values in maximum-parsimony and neighbor-joining analyses and were confirmed by the maximum-likelihood method. The nucleotide diversity between the 73 HIV-1C isolates (mean value of 8.93%; range, 2.9 to 11.7%) was significantly higher than the diversity of the samples to the consensus sequence (mean value of 4.86%; range, 3.3 to 7.2%, P < 0.0001). The translated amino acid distances to the consensus sequence were significantly lower than distances between samples within all HIV-1C proteins. The consensus sequences of HIV-1C proteins accompanied by amino acid frequencies were presented (that of Gag is presented in this work; those of Pol, Vif, Vpr, Tat, Rev, Vpu, Env, and Nef are presented elsewhere [http://www.aids.harvard.edu/lab_research/concensus_sequence.htm]). Additionally, in the promoter region three NF-{kappa}B sites (GGGRNNYYCC) were identified within the consensus sequences of the entire set or any subset of HIV-1C isolates. This study suggests that the consensus sequence approach could overcome the high genetic diversity of HIV-1C and facilitate an AIDS vaccine design, particularly if the assumption that an HIV-1C antigen with a more extensive match to the circulating viruses is likely to be more efficacious is proven in efficacy trials.

* Corresponding author. Mailing address: Department of Immunology and Infectious Diseases, Harvard School of Public Health, FXB-402, 651 Huntington Ave., Boston, MA 02115. Phone: (617) 432-0975. Fax: (617) 739-8348. E-mail: messex{at}hsph.harvard.edu.

Journal of Virology, June 2002, p. 5435-5451, Vol. 76, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.11.5435-5451.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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