Feng Xuan, Heyden Nancy Vander, Ratner Lee
Departments of Medicine, Pathology, and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Virol. 2003 Dec;77(24):13389-95. doi: 10.1128/jvi.77.24.13389-13395.2003.
Alpha-2a interferon (IFN-alpha2a) has beneficial clinical effects on human T-cell leukemia virus type 1 (HTLV-1) infection, but its antiviral mechanism of action is unknown. Antiviral effects of IFN-alpha2a were studied in 293T cells expressing HTLV-1 proviral DNA and in HTLV-1-infected cells (HOS/PL, MT2, and HUT102). In 293T cells, an 50% inhibitory concentration of 10 U of IFN-alpha2a/ml was determined by p19 antigen ELISA. Analysis of IFN-treated cells demonstrated no defect in viral protein synthesis but did show a decrease in the level of released virus, as determined by immunoblot assays. Electron microscopy studies of IFN-treated cells revealed neither a defect in the site of virus budding nor tethering of virus particles at the plasma membrane, thus arguing against an effect on virus release. Cell fractionation studies and confocal microscopy showed no effect of IFN on Gag association with membranes. However, the level of Gag association with lipid rafts was decreased, suggesting a role of IFN in inhibiting HTLV-1 assembly.
α-2a干扰素（IFN-α2a）对人类1型嗜T细胞白血病病毒（HTLV-1）感染具有有益的临床效果，但其抗病毒作用机制尚不清楚。在表达HTLV-1前病毒DNA的293T细胞以及HTLV-1感染的细胞（HOS/PL、MT2和HUT102）中研究了IFN-α2a的抗病毒作用。在293T细胞中，通过p19抗原ELISA测定出IFN-α2a的50%抑制浓度为10 U/ml。对经IFN处理的细胞进行分析，结果表明病毒蛋白合成无缺陷，但通过免疫印迹分析确实显示释放病毒的水平有所降低。对经IFN处理的细胞进行电子显微镜研究，既未发现病毒出芽位点存在缺陷，也未发现病毒颗粒在质膜处的 tethering（此处原文tethering含义不明，可能是“束缚”之类意思），因此排除了对病毒释放的影响。细胞分级分离研究和共聚焦显微镜检查显示IFN对Gag与膜的结合没有影响。然而，Gag与脂筏的结合水平降低，提示IFN在抑制HTLV-1组装中发挥作用。
