摘要
干扰素诱导跨膜蛋白(interferon inducible transmembrane proteins,IFITM)是20世纪80年代人们通过小干扰RNA技术研究中发现的一种抗病毒蛋白,目前该蛋白的抗病毒作用及其机制已成为研究热点。迄今的研究发现,IFITM的抗甲型病毒感染作用是通过多种途径实现的。IFTIM能够有效作用于甲型流感病毒表面糖蛋白血凝素与宿主细胞表面受体结合之后、流感病毒包膜与内吞形成的胞内体膜融合之前的流感病毒感染的胞内体途径。在该作用过程中,IFITM下调网格蛋白的表达,扰乱液泡ATP酶(V型ATP酶,vacuolar ATPase,v-ATPase)的酸化功能,破坏胞内体胆固醇的平衡,从而抑制病毒包膜与胞内体膜融合,阻断病毒RNA释放到细胞质中。此外,IFITM也能够影响感染细胞与正常细胞之间的半融合,发挥抑制病毒感染的作用。近年来的研究提示,IFITM通过诱导记忆T细胞选择性高表达该蛋白,继而保护细胞免受甲型流感病毒感染。
interferon inducible transmembrane proteins(IFITM) were identified by small interference RNA(siRNA) screening method in 1980s. Its antiviral effect and mechanism have become a research hotspot in recent years. Recent studies have shown that IFITM could block the entry of viruses by multiple pathways. It could restrict the endosomal pathway in influenza A viral replication cy- cle after viral host binding but prior to viral RNA release. In the endosomal pathway, IFITM inhibited the viral RNA release to cyto- plasm by decreasing the expression of clathrin, disturbing the acidified function of vacuolar (v)-ATPase, and disrupting intracellular cholesterol homeostasis. Some reports showed that IFITM could restrict the hemifusion between infectious cells and uninfectious cells. Moreover, IFITM could also induce the memory CD8 ~ T cells to selectively maintaining the expression of themselves, thus enhancing the survival of cells.
出处
《国际药学研究杂志》
CAS
CSCD
2013年第6期757-764,共8页
Journal of International Pharmaceutical Research
关键词
干扰素诱导跨膜蛋白
甲型流感病毒
胞内体途径
抗病毒作用机制
interferon inducible transmembrane proteins
influenza A virus
endosomal pathway
antiviral mechanisms