More than meets the I: the diverse antiviral and cellular functions of interferon-induced transmembrane proteins.
More than meets the I: the diverse antiviral and cellular functions of interferon-induced transmembrane proteins.
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DOI：
10.1186/s12977-017-0377-y
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发表时间：
2017-11-21
期刊：
影响因子：
3.3
通讯作者：
Compton AA
中科院分区：
文献类型：
--
作者：
Shi G;Schwartz O;Compton AA
人类抗病毒免疫的第一反应者是驻留在我们每个细胞内的固有免疫反应的组成部分。这个细胞自主的武器库由核酸传感器和抗病毒效应器组成，进化具有战略意义地放置这些传感器来检测和限制入侵的病毒。虽然一些因子存在于基线上，以允许对细胞内部进行持续监测，但另一些因子则被细胞因子(如干扰素)上调，这些细胞因子发出邻近细胞正在进行病毒感染的信号。在这篇综述中，我们强调了干扰素诱导的跨膜蛋白(IFITM)在病毒感染过程中所扮演的多重角色，重点是IFITM3和HIV-1。此外，我们还讨论了IFITM蛋白相互交织的细胞途径，以及它们在感染环境之外的各种功能。虽然被认为是在细胞培养和体内预防病毒感染和致病的广泛作用的、有效的限制因素，但关于它们在某些病毒环境中的确切作用方式和重要性仍然存在问题。对IFITM蛋白功能的持续研究将进一步巩固它们作为病毒易感性的关键宿主决定因素的地位，并在新的抗病毒疗法的开发中优先考虑它们。
The first responders of human antiviral immunity are components of the intrinsic immune response that reside within each and every one of our cells. This cell-autonomous arsenal consists of nucleic acid sensors and antiviral effectors strategically placed by evolution to detect and restrict invading viruses. While some factors are present at baseline to allow for constant surveillance of the cell interior, others are upregulated by cytokines (such as interferons) that signal a viral infection underway in neighboring cells. In this review, we highlight the multiple roles played by the interferon-induced transmembrane (IFITM) proteins during viral infection, with focuses on IFITM3 and HIV-1. Moreover, we discuss the cellular pathways in which IFITM proteins are intertwined and the various functions they have been ascribed outside the context of infection. While appreciated as broadly-acting, potent restriction factors that prevent virus infection and pathogenesis in cell culture and in vivo, questions remain regarding their precise mode of action and importance in certain viral contexts. Continued efforts to study IFITM protein function will further cement their status as critical host determinants of virus susceptibility and prioritize them in the development of new antiviral therapies.
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