Mwimanzi, PhilipMarkle, Tristan JMartin, EricOgata, YokoKuang, Xiaomei TTokunaga, MichiyoMahiti, MacdonaldPereyra, FMiura, ToshiyukiWalker, BruceBrumme, Zabrina LBrockman, Mark AUeno, Takamasa2013-05-092013Mwimanzi, Philip, Tristan J. Markle, Eric Martin, Yoko Ogata, Xiaomei T. Kuang, Michiyo Tokunaga, Macdonald Mahiti, and et al. 2013. Attenuation of multiple Nef functions in HIV-1 elite controllers. Retrovirology 10:1.1742-4690http://nrs.harvard.edu/urn-3:HUL.InstRepos:10613651Background: 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.en-USHIV-1NefHuman Leukocyte Antigen (HLA) class IHLA-B*57elite controllersimmune escapereplication capacityJournal Article2013-05-0910.1186/1742-4690-10-1