%0 Journal Article
%T Attenuation of multiple Nef functions in HIV-1 elite controllers
%A Mwimanzi Philip
%A Markle Tristan J
%A Martin Eric
%A Ogata Yoko
%J Retrovirology
%D 2013
%I BioMed Central
%R 10.1186/1742-4690-10-1
%X Background Impaired HIV-1 Gag, Pol, and Env function has been described in elite controllers (EC) who spontaneously suppress plasma viremia to < 50 RNA copies/mL; however, activity of the accessory protein Nef remains incompletely characterized. We examined the ability of 91 Nef clones, isolated from plasma of 45 EC and 46 chronic progressors (CP), to down-regulate HLA class I and CD4, up-regulate HLA class II invariant chain (CD74), enhance viral infectivity, and stimulate viral replication in PBMC. Results In general, EC Nef clones were functional; however, all five activities were significantly lower in EC compared to CP. Nef clones from HLA-B*57-expressing EC exhibited poorer CD4 down-regulation function compared to those from non-B*57 EC, and the number of EC-specific B*57-associated Nef polymorphisms correlated inversely with 4 of 5 Nef functions in these individuals. Conclusion Results indicate that decreased HIV-1 Nef function, due in part to host immune selection pressures, may be a hallmark of the EC phenotype.
%K HIV-1
%K Nef
%K Elite controllers
%K Human Leukocyte Antigen (HLA) class I
%K Immune escape
%K Replication capacity
%K HLA-B*57
%U http://www.retrovirology.com/content/10/1/1