Amino acids at positions 3, 168, and 169 are associated with the ability of Nef proteins from HIV-1 CRF01_AE to downmodulate CD4
Amino acids at positions 3, 168, and 169 are associated with the ability of Nef proteins from HIV-1 CRF01_AE to downmodulate CD4
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位点 3、168 和 169 的氨基酸与 HIV-1 CRF01_AE 的 Nef 蛋白下调 CD4 的能力相关
DOI：
10.1002/jmv.24851
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发表时间：
2017
影响因子：
12.7
通讯作者：
Wang Jian-Hua
中科院分区：
文献类型：
--
作者：
Kuang Wen-Dong;Zhou Yan-Heng;Zhong Ping;Zhang Chiyu;Wang Jian-Hua
在中国，几种HIV-1亚型在各种高危人群中共同传播，近年来在MSM（男男性行为者）中观察到CRF01_AE的患病率增加。感染CRF01_AE的患者可能比感染非CRF01_AE的患者经历更快的疾病进展;然而，潜在机制仍然难以捉摸。HIV-1 Nef是一种多功能蛋白，在病毒发病机制中起着关键作用。Nef下调CD 4和人类白细胞抗原（HLA），以促进病毒传播和逃避宿主免疫反应。在这项研究中，我们研究了从HIV-1 CRF01_AE中分离的Nef蛋白的CD 4下调活性，并分析了Nef下调CD 4的能力与疾病进展的潜在关系。我们发现，来自HIV-1 CRF01_AE的大多数Nef有效下调了CD 4; CD 4下调活性较弱的Nef往往与较高的CD 4水平和较低的病毒载量相关。进一步阐明揭示了CRF01_AE Nef的位置3、168和169处的氨基酸残基与下调CD 4的能力相关。我们的数据表明，Nef介导的CD 4下调能力不是控制疾病进展的唯一决定因素，应考虑其他宿主和病毒因素来解释HIV-1 CRF01_AE感染患者的快速疾病进展。
Several HIV‐1 subtypes are co‐circulating among various high‐risk groups in China, and an increasing prevalence of CRF01_AE was observed among MSM (men who have sex with men) within recent years. Patients infected with CRF01_AE may experience a more rapid disease progression than patients infected with non‐CRF01_AE; however, the underlying mechanisms remains elusive. HIV‐1 Nef is a multifunctional protein and plays critical roles in viral pathogenesis. Nef downregulates CD4 and human leukocyte antigen (HLA) to promote viral transmission and escape from the host immune response. In this study, we investigated the CD4 downmodulation activity of Nef proteins isolated from HIV‐1 CRF01_AE and analyzed a potential relationship of Nef's capacity to downregulate CD4 with disease progression. We found that the majority of these Nefs from HIV‐1 CRF01_AE efficiently downregulated CD4; Nefs with weaker CD4 downmodulation activity tended to be associated with higher CD4 levels and lower viral loads. Further elucidation revealed that amino acid residues at positions 3, 168, and 169 of CRF01_AE Nefs were associated with the capacity to downregulate CD4. Our data suggest that the capacity of Nef‐mediated CD4 downregulation is not the only determinant for controlling disease progression, and other host and viral factors should be considered to explain the rapid disease progression of patients infected with HIV‐1 CRF01_AE.