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- 3 phylogenetic correction methods---MLL (maximum likelihood character state analysis followed by likelihood ratio test), MLF (maximum likelihood character state analysis followed by Fisher test), and parsimony character state analysis were used to identify points in the HIV-1 subtype C proteome that conferred susceptibility or resistance to CTLs. Associations of HLA-epitope combinations that were inferred to be susceptible or resistant were organized into immunological sets that would help identify the best residues and genes as candidates for vaccines. While all proteins were interrogated, Gag, Pol, Env and Nef were focused upon. Amino acid changes were evaluated for association with plasma viral load.
- Proteome maps may be seen at http://www.hiv.lanl.gov/content/immunology/hlatem/study5/index.html with information showing single or multiple sites involving escape and reversion.
- HLA- B and -C alleles associated more with aa changes than HLA-A, suggesting that the former two are more important in driving viral evolution.
- The ratio of susceptible to resistant residues in HIV proteins was in descending order, Vpr>Gag>Rev>Pol>Nef>Vif>Tat>Env>Vpu, showing that epitopes from the earlier proteins are more conserved owing to viral fitness cost upon mutation.
- This previously described Vif HLA B*1503-restricted epitope, SKRASGWFF was susceptible at K2. Variants SgRASGWFF, SqRASGWFF and SrRASGWFF were resistant to CTL response, but associated with lower viral loads. This epitope is 1 of 7 that suggest a fitness cost to immune escape.
Christine M. Rousseau, Marcus G. Daniels, Jonathan M. Carlson, Carl Kadie, Hayley Crawford, Andrew Prendergast, Philippa Matthews, Rebecca Payne, Morgane Rolland, Dana N. Raugi, Brandon S. Maust, Gerald H. Learn, David C. Nickle, Hoosen Coovadia, Thumbi Ndung'u, Nicole Frahm, Christian Brander, Bruce D. Walker, Philip J. R. Goulder, Tanmoy Bhattacharya, David E. Heckerman, Bette T. Korber, and James I. Mullins. HLA Class I-Driven Evolution of Human Immunodeficiency Virus Type 1 Subtype C Proteome: Immune Escape and Viral Load. J. Virol., 82(13):6434-6446, Jul 2008. PubMed ID: 18434400.
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