Attenuation of Multiple Nef Functions in HIV-1 Elite Controllers

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Attenuation of Multiple Nef Functions in HIV-1 Elite Controllers

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Title: Attenuation of Multiple Nef Functions in HIV-1 Elite Controllers
Author: Mwimanzi, Philip; Markle, Tristan J; Martin, Eric; Ogata, Yoko; Kuang, Xiaomei T; Tokunaga, Michiyo; Mahiti, Macdonald; Pereyra, Florencia M.; Miura, Toshiyuki; Walker, Bruce David; Brumme, Zabrina L; Brockman, Mark A; Ueno, Takamasa

Note: Order does not necessarily reflect citation order of authors.

Citation: Mwimanzi, 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.
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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.
Published Version: doi:10.1186/1742-4690-10-1
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