Attenuation of multiple Nef functions in HIV-1 elite controllers
P Mwimanzi, TJ Markle, E Martin, Y Ogata, XT Kuang… - Retrovirology, 2013 - Springer
Retrovirology, 2013•Springer
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 …
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 …
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.
Springer
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