Crimean-Congo hemorrhagic fever virus utilizes a clathrin- and early endosome-dependent entry pathway
Crimean-Congo hemorrhagic fever virus utilizes a clathrin- and early endosome-dependent entry pathway
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DOI：
10.1016/j.virol.2013.05.030
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发表时间：
2013-09-01
期刊：
影响因子：
3.7
通讯作者：
Schmaljohn, Connie S.
中科院分区：
文献类型：
--
作者：
Garrison, Aura R.;Radoshitzky, Sheli R.;Schmaljohn, Connie S.
克里米亚-刚果出血热病毒（CCHFV）的早期事件尚未完全确定。早期的研究表明，CCHFV可能通过网格蛋白介导的内吞作用（CME）进入细胞。在这里，我们提供了CME条目的确证性证据表明，CCHFV感染的Pitstop 2，一种药物，特异性和可逆地干扰网格蛋白包被的凹坑的动力学处理的细胞受到抑制。此外，我们表明，CCHFV感染抑制siRNA耗尽网格蛋白坑相关蛋白AP-2。CME进入后，我们表明，CCHFV有一个pH依赖性的进入步骤，与病毒灭活发生在pH 6.0及以下。为了更精确地定义CCHFV的内体运输，我们首次表明Rab 5蛋白而不是Rab 7蛋白的显性阴性形式的过表达抑制CCHFV感染。这些结果表明，CCHFV可能通过早期内体组分进入细胞。爱思唯尔公司出版
The early events in Crimean-Congo hemorrhagic fever virus (CCHFV) have not been completely characterized. Earlier work indicated that CCHFV likely enters cells by clathrin-mediated endocytosis (CME). Here we provide confirmatory evidence for CME entry by showing that CCHFV infection is inhibited in cells treated with Pitstop 2, a drug that specifically and reversibly interferes with the dynamics of clathrin-coated pits. Additionally, we show that CCHFV infection is inhibited by siRNA depletion of the clathrin pit associated protein AP-2. Following CME entry, we show that CCHFV has a pH-dependent entry step, with virus inactivation occurring at pH 6.0 and below. To more precisely define the endosomal trafficking of CCHFV, we show for the first time that overexpression of the dominant negative forms of Rab5 protein but not Rab7 protein inhibits CCHFV infection. These results indicate that CCHFV likely enters cells through the early endosomal compalunent. Published by Elsevier Inc.