HIV-Drug Resistance Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Virology. 2013 Feb 5;436(1):201-9. doi: 10.1016/j.virol.2012.11.012. Epub 2012 Dec 20.
Tetherin is part of the cellular innate immunity and impedes cell-free transmission of viruses that bud from the plasma membrane by retaining them on the cell surface. Some viruses have evolved activities in different proteins such as Vpu (HIV-1), K-protein (KSHV), Nef (SIV) or Env (HIV-2) to downregulate tetherin and overcome its restriction. We found that chronically HTLV-1 infected T-cell lines express eightfold more tetherin than uninfected transformed T-cell lines suggesting that tetherin expression is not inhibited by the virus. We observed that even small amounts of exogenous tetherin caused the retention of HTLV-1 on the cell surface and severely reduced cell-free infectivity of HTLV-1, but that cell-cell transmission, which is more relevant for HTLV-1, was significantly less decreased. However, knock-down of tetherin expresssion resulted in a slight increase in cell-cell infection indicating that the protein does not enhance this route of transmission.
Tetherin 是细胞固有免疫的一部分,通过将病毒保留在细胞表面上来阻碍从质膜出芽的游离病毒的传播。一些病毒已经进化出不同蛋白质中的活性,例如 Vpu(HIV-1)、K 蛋白(KSHV)、Nef(SIV)或 Env(HIV-2),以下调 tetherin 并克服其限制。我们发现,慢性 HTLV-1 感染的 T 细胞系比未感染的转化 T 细胞系表达高出八倍的 tetherin,这表明病毒不会抑制 tetherin 的表达。我们观察到,即使少量的外源性 tetherin 也会导致 HTLV-1 在细胞表面的滞留,并严重降低 HTLV-1 的游离感染性,但与 HTLV-1 更相关的细胞间传播则显著减少。然而,tetherin 表达的敲低导致细胞间感染略有增加,表明该蛋白不会增强这种传播途径。