Open Access Highly Accessed Research

Attenuation of multiple Nef functions in HIV-1 elite controllers

Philip Mwimanzi12, Tristan J Markle2, Eric Martin2, Yoko Ogata1, Xiaomei T Kuang2, Michiyo Tokunaga1, Macdonald Mahiti1, Florencia Pereyra3, Toshiyuki Miura4, Bruce D Walker3, Zabrina L Brumme25, Mark A Brockman25* and Takamasa Ueno1*

Author Affiliations

1 Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto, 860-0811, Japan

2 Simon Fraser University, Burnaby, BC, Canada

3 Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Boston, MA, USA

4 University of Tokyo, Tokyo, Japan

5 British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada

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Retrovirology 2013, 10:1  doi:10.1186/1742-4690-10-1

Published: 7 January 2013

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.

Keywords:
HIV-1; Nef; Elite controllers; Human Leukocyte Antigen (HLA) class I; Immune escape; Replication capacity; HLA-B*57