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- Title
Attenuation of multiple Nef functions in HIV-1 elite controllers.
- Authors
Mwimanzi, Philip; Markle, Tristan J.; Martin, Eric; Ogata, Yoko; Kuang, Xiaomei T.; Tokunaga, Michiyo; Mahiti, Macdonald; Pereyra, Florencia; Miura, Toshiyuki; Walker, Bruce D.; Brumme, Zabrina L.; Brockman, Mark A.; Ueno, Takamasa
- 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.
- Subjects
HIV; NEF gene; HLA histocompatibility antigens; VIRUS diseases; VIREMIA; PHENOTYPES; PATIENTS
- Publication
Retrovirology, 2013, Vol 10, Issue 1, p1
- ISSN
1742-4690
- Publication type
Article
- DOI
10.1186/1742-4690-10-1