AEGiS-14IAC: Variability in HIV-1 subtype C protease cleavage sites, an indication of viral fitness ?

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Variability in HIV-1 subtype C protease cleavage sites, an indication of viral fitness ?

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no.. A10040)

Engelbrecht S, de Oliveira TP, Cassol S, Megede JZ, Barnett SW, van Rensburg EJ
University of Stellenbosch and Tygerberg Hospital, Cape Town, South Africa

BACKGROUND: HIV-1 subtype C viruses are the most commonly transmitted subtype worldwide and are causing explosive epidemics in Southern Africa, India and China. We hypothesize that the flexibility of the protease may be one of the factors enhancing the fitness of subtype C viruses.

METHODS: The protease cleavage site mutation profiles of full-length genomes from a subtype B (n=28), a subtype C (n=27) and a group M (n=27) dataset, were evaluated. Phylogenetic analysis was done to determine constraints between cleavage sites and HIV subtypes and positive selection were investigated by Dn/Ds ratios.

RESULTS: The most variable cleavage sites were within p2 and NC in the gag, and within the p6pol / PR and NEF genes and the number of substitutions decreased in the positions near the cleavage sites. Phylogenetic analysis supported subtype clustering with high bootstrap values.

CONCLUSION: Thus subtype C viruses analysed in this study showed a higher site-specific variability compared to the other HIV-1 subtype B and Group M subset sequences, representing 11 different subtypes. The presence of positive selected sites in subtype C could influence the flexibility of the protease to recognize and select specific sites that produce a better catalytic efficiency and better viral fitness.

Keywords: AEGIS, HIV Protease, HIV-1, HIV Infections, China, HIV Protease Inhibitors, HIV Seropositivity, HIV-1 Reverse Transcriptase, India, Africa, Southern, virology

020707
A10040