Abstract:
Abstract
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.
