Journal of Bioequivalence & Bioavailability

Analysis of the HIV-1 nef gene for possible therapeutics during HIV infection

3^rd World Congress Bioavailability & Bioequivalence

March 26-28, 2012 Marriott Hotel & Convention Centre, Hyderabad, India

Gaurav Shrivastava and Shailendra K. Saxena

Posters: J Bioequiv Availab

Abstract:

A IDS is an immune system disease with a viral etiology. HIV Nef, accessory factor of HIV, is a 27-kDa regulatory protein that interacts with several host cellular proteins resulting in increase in viral replication and the impairment of both innate and adaptive immune responses. Unfortunately, although Nef plays an important role in AIDS pathogenesis, no Nef-inhibiting drugs are currently available. Thus, finding anti-Nef compounds would contribute to innovative anti-HIV therapeutic approaches. A likely key factor in the failure of a HIV-1 vaccine based on cytotoxic T lymphocytes (CTL) is the natural immunodominance of epitopes that fall in variable regions of the proteome, which both increases the chance of epitope sequence mismatch with the incoming challenge strain and replicates the pathogenesis of early CTL failure due to epitope escape mutation during natural infection. To identify potential vaccine sequences to focus the CTL response on highly conserved epitopes, the whole proteomes of HIV-1 clade B and C were assessed for Shannon entropy at each amino acid position. Highly conserved regions in Nef (Nef 101?150) were identified across clades. Inter- and intra-clade variability of amino acids within the regions tended to overlap, suggesting that polyvalent representation of consensus sequences for HIV-1 clade B and C would allow broad HIV-1 clade representation. Our data suggest that vaccine delivery of a mixture of these regions could focus the CTL response against conserved epitopes that are broadly representative of circulating HIV-1 strains