Division of Infection and Immunity, Joint Research Center for Human Retrovirus Infection Kumamoto University , Kumamoto, Japan.
Graduate School of Medical Sciences, Kumamoto University , Kumamoto, Japan.
J Virol. 2023 Oct 31;97(10):e0082323. doi: 10.1128/jvi.00823-23. Epub 2023 Sep 28.
Pathogenesis of HIV-1 is enhanced through several viral-encoded proteins that counteract a range of host restriction molecules. HIV-1 Nef counteracts the cell membrane protein SERINC5 by downregulating it from the cell surface, thereby enhancing virion infectivity. Some subtype B reference Envelope sequences have shown the ability to bypass SERINC5 infectivity restriction independent of Nef. However, it is not clear if and to what extent circulating HIV-1 strains can exhibit resistance to SERINC5 restriction. Using a panel of Envelope sequences isolated from 50 Tanzanians infected with non-B HIV-1 subtypes, we show that the lentiviral reporters pseudotyped with patient-derived Envelopes have reduced sensitivity to SERINC5 and that this sensitivity differed among viral subtypes. Moreover, we found that SERINC5 sensitivity within patient-derived Envelopes can be modulated by separate regions, highlighting the complexity of viral/host interactions.
HIV-1 的发病机制是通过几种病毒编码的蛋白来增强的，这些蛋白可以对抗一系列宿主限制分子。HIV-1 的 Nef 通过下调细胞膜蛋白 SERINC5 来从细胞表面将其下调，从而增强病毒粒子的感染力。一些 B 亚型参考包膜序列已经显示出具有绕过 SERINC5 感染限制的能力，而不依赖于 Nef。然而，目前尚不清楚循环 HIV-1 株是否以及在何种程度上能够表现出对 SERINC5 限制的抗性。我们使用一组来自 50 名感染非 B 型 HIV-1 亚型的坦桑尼亚人的包膜序列，我们发现用患者衍生的包膜假型化的慢病毒报告器对 SERINC5 的敏感性降低，并且这种敏感性在不同的病毒亚型之间存在差异。此外，我们发现患者衍生包膜中的 SERINC5 敏感性可以通过单独的区域来调节，突出了病毒/宿主相互作用的复杂性。
