Alpha interferon inhibits human T-Cell leukemia virus type 1 assembly by preventing Gag interaction with rafts
Alpha interferon inhibits human T-Cell leukemia virus type 1 assembly by preventing Gag interaction with rafts
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DOI：
10.1128/jvi.77.24.13389-13395.2003
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发表时间：
2003-12-01
影响因子：
5.4
通讯作者：
Ratner, L
中科院分区：
文献类型：
--
作者：
Feng, X;Heyden, NV;Ratner, L
α-2a干扰素（IFN-α 2a）对人类T细胞白血病病毒1型（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293 T细胞和HTLV-1感染的细胞（HOS/PL、MT 2和HUT 102）中研究了IFN-α 2a的抗病毒作用。在293 T细胞中，通过p19抗原ELISA测定10 U IFN-α 2a/ml的50%抑制浓度。IFN-处理的细胞的分析表明，在病毒蛋白质合成没有缺陷，但确实显示了释放的病毒，如通过免疫印迹测定的水平下降。电子显微镜研究IFN处理的细胞既没有发现缺陷的病毒出芽的网站，也没有拴系的病毒颗粒在质膜，从而反对对病毒释放的影响。细胞分级分离研究和共聚焦显微镜显示干扰素对Gag与膜的结合没有影响。然而，Gag与脂筏的结合水平降低，表明IFN在抑制HTLV-1组装中的作用。
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.