AEGiS-13IAC: Evidence for potential adaptive evolution of HIV-1C in Southern Africa.

13th International AIDS Conference


Durban, South Africa - July 9-July 14, 2000

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Evidence for potential adaptive evolution of HIV-1C in Southern Africa.

Int Conf AIDS 2000 Jul 9-14; 13:33 (abstract no.. LbPeA7007)

Montano M, Essex M
Harvard AIDS Institute, Boston, MA 02115. Fax: 617-739-8348, E-mail: mmontano@hsph.harvard.edu.

Background and

METHODS: Despite the extraordinary amount of HIV-1 genetic diversity within individuals and populations that has identified the global presence of at least 11 subtypes (A-K), the potential link between genetic change, subtype configuration and an adaptive phenotype remains unclear. To assess the potential for adaptive evolution we have analyzed the promoter region of HIV-1C isolates from southern Africa in response to the pro-inflammatory cytokine TNF-α and we have used a homology based molecular modelling approach (InsightII) to develop a "structural signature" for the predicted three dimensional impact of subtype specific changes in the Tat and Nef proteins.

RESULTS: Functional analysis the enhancer region within the long terminal repeat (LTR) indicated that HIV-1C isolates have at least threee NF-kappaB binding sites, unlike other subtypes, which have only 1 or 2 sites. A correlation was shown between NF-kappaB enhancer configuration and responsiveness to the proinflammatory cytokine tumor necrosis factor (TNF)-α. Modelling of Tat and Nef proteins revealed evidence for patient and subtype specific differences that suggest the potential for structurally adaptive amino acid changes.

CONCLUSIONS: The naturally occurring gain-of-function in the NF-kappaB enhancer of HIV-1C observed in this study may provide an advantage for the HIV-1C virus in vivo, particularly in the presence of pro-inflammatory cytokines associated with prevalent STDs in southern Africa. The presence of potentially non-random amino acid changes may also suggest that adaptive subtype specific changes have occurred in these proteins and warrant further study.

Keywords: AEGIS, HIV Infections, HIV-1, NF-kappa B, HIV Seropositivity, Africa, Southern, Enhancer Elements (Genetics), Promoter Regions (Genetics), Terminal Repeat Sequences, Tumor Necrosis Factor, tumor necrosis factor precursor, Human, genetics, AIDSKWDaegis,hivinfections,hiv-1,nf-kappab,hivseropositivity,africa,southern,enhancerelements(genetics),promoterregions(genetics),terminalrepeatsequences,tumornecrosisfactor,tumornecrosisfactorprecursor,human,genetics,aids
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LbPeA7007

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