Institute of Virology, Helmholtz Zentrum Munich, Munich, Germany.
Institute of Medical Virology, University Hospital Tuebingen, Tübingen, Germany.
J Int AIDS Soc. 2017 Sep 19;20(1):21865. doi: 10.7448/IAS.20.1.21865.
Restriction factors (RFs) suppress HIV-1 in cell lines and primary cell models. Hence, RFs might be attractive targets for novel antiviral strategies, but their importance for virus control is controversial.
We profiled the expression of RFs in primary blood-derived mononuclear cells (PBMC) from therapy-naïve HIV-1 patients and quantified infection.
Overall, there was no correlation between individual RF expression and HIV-1 status in total PBMC. However, we identified a T cell population with low levels of intracellular CD2 and reduced expression of SAMHD1, p21 and SerinC5. CD2 T cells with reduced RF expression were markedly positive for HIV-1 p24. In contrast, CD2+ T cells were less infected and expressed higher levels of RFs. CD2 T cell infection correlated with viral loads and was associated with HIV-1 disease progression.
In untreated therapy naïve chronic HIV-1 patients, RF expression in T cells is associated with CD2 expression and seems to influence viral loads. Our study suggests that RFs help to control HIV-1 infection in certain T cells and supports the potential for RFs as promising targets for therapeutic intervention.
限制因子 (RFs) 可抑制细胞系和原代细胞模型中的 HIV-1。因此，RFs 可能成为新型抗病毒策略的有吸引力的靶点，但它们对病毒控制的重要性存在争议。
我们分析了来自未经治疗的 HIV-1 患者的原代血液衍生单核细胞 (PBMC) 中 RFs 的表达，并对感染进行了定量。
总体而言，在总 PBMC 中，个体 RF 表达与 HIV-1 状态之间没有相关性。然而，我们鉴定了一个 T 细胞群体，其细胞内 CD2 水平较低，SAMHD1、p21 和 SerinC5 的表达降低。表达降低的 RF 的 CD2 T 细胞对 HIV-1 p24 呈明显阳性。相比之下，CD2+T 细胞感染较少，并且表达更高水平的 RFs。CD2 T 细胞感染与病毒载量相关，并与 HIV-1 疾病进展相关。
在未经治疗的初治慢性 HIV-1 患者中，T 细胞中的 RF 表达与 CD2 表达相关，似乎影响病毒载量。我们的研究表明，RFs 有助于控制某些 T 细胞中的 HIV-1 感染，并支持 RFs 作为有前途的治疗干预靶点的潜力。
