Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
Retrovirology. 2013 Jan 7;10:1. doi: 10.1186/1742-4690-10-1.
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.
In general, EC Nef clones were functional; however, all five activities were significantly lower in EC compared to CP. Nef clones from HLA-B57-expressing EC exhibited poorer CD4 down-regulation function compared to those from non-B57 EC, and the number of EC-specific B*57-associated Nef polymorphisms correlated inversely with 4 of 5 Nef functions in these individuals.
Results indicate that decreased HIV-1 Nef function, due in part to host immune selection pressures, may be a hallmark of the EC phenotype.
在自发抑制血浆病毒载量至 < 50 RNA 拷贝/mL 的精英控制者（EC）中，已经描述了 HIV-1 Gag、Pol 和 Env 功能受损；然而，辅助蛋白 Nef 的活性仍未完全表征。我们检测了来自 45 名 EC 和 46 名慢性进展者（CP）血浆的 91 个 Nef 克隆，以评估其下调 HLA Ⅰ类和 CD4、上调 HLA Ⅱ类不变链（CD74）、增强病毒感染力以及刺激 PBMC 中病毒复制的能力。
一般来说，EC Nef 克隆具有功能；然而，与 CP 相比，所有 5 种活性在 EC 中均显著降低。与非 B57 EC 相比，来自 HLA-B57 表达的 EC 的 Nef 克隆表现出较差的 CD4 下调功能，而这些个体中与 5 种 Nef 功能中的 4 种呈负相关的 EC 特异性 B*57 相关 Nef 多态性的数量。
结果表明，HIV-1 Nef 功能的降低，部分归因于宿主免疫选择压力，可能是 EC 表型的一个标志。
