Crimean-Congo hemorrhagic fever virus entry into host cells occurs through the multivesicular body and requires ESCRT regulators.
Crimean-Congo hemorrhagic fever virus entry into host cells occurs through the multivesicular body and requires ESCRT regulators.
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Crimean-Congo出血热病毒进入宿主细胞是通过多囊体发生的，需要ESCRT调节剂。
DOI：
10.1371/journal.ppat.1004390
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发表时间：
2014-09
期刊：
影响因子：
6.7
通讯作者：
Davey RA
中科院分区：
文献类型：
--
作者：
Shtanko O;Nikitina RA;Altuntas CZ;Chepurnov AA;Davey RA
克里米亚-刚果出血热病毒（CCHFV）是一种蜱传布尼亚病毒，可在人类中引起严重疾病暴发，致死率接近30%。目前还没有被广泛接受的治疗方法来预防或治疗这种疾病。CCHFV通过网格蛋白介导的内吞作用进入宿主细胞，随后被运送到酸化的隔室，在那里病毒包膜与细胞膜融合。为了更好地了解摄取途径，我们试图确定控制CCHFV通过细胞运输的宿主因子。我们证明，在以rab5依赖的方式通过早期核内体后，CCHFV被递送到多泡体（MVBs）。病毒颗粒在感染后约1小时定位于MVBs，并影响细胞器在细胞内的分布。有趣的是，阻断Rab7活性对病毒与MVBs的关联没有影响。产性病毒感染依赖于磷脂酰肌醇3-激酶（PI3K）的活性，PI3K介导了功能性MVBs的形成。沉默控制mchfv生物发生的内体转运（ESCRT）途径所需的Tsg101、Vps24、Vps4B或Alix/Aip1组分，抑制野生型病毒以及携带CCHFV糖蛋白的新型假型水疱性口炎病毒（VSV）的感染，支持MVB途径在CCHFV进入中的作用。我们进一步证明，阻断MVBs的运输仍然允许病毒进入，同时阻止膜融合所需的囊泡酸化，将病毒粒子捕获在MVBs中。这些发现表明MVBs是感染所必需的，并且是病毒-核内体膜融合的位点。克里米亚-刚果出血热病毒（CCHFV）是一种严重的、通常是致命的人类疾病的病因。虽然已经证明CCHFV进入细胞依赖于网格蛋白介导的内吞作用、低pH值和早期核内体，但病毒进入细胞质启动基因组复制的核内体的身份尚不清楚。在这里，我们发现CCHFV通过早期核内体转运到多泡体（MVBs）。我们还发现MVBs可能是病毒在进入细胞质之前遇到的最后一个细胞器。我们的工作已经确定了CCHFV进入所必需的新细胞因子和针对该病原体的治疗干预的潜在新靶点。
Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne bunyavirus causing outbreaks of severe disease in humans, with a fatality rate approaching 30%. There are no widely accepted therapeutics available to prevent or treat the disease. CCHFV enters host cells through clathrin-mediated endocytosis and is subsequently transported to an acidified compartment where the fusion of virus envelope with cellular membranes takes place. To better understand the uptake pathway, we sought to identify host factors controlling CCHFV transport through the cell. We demonstrate that after passing through early endosomes in a Rab5-dependent manner, CCHFV is delivered to multivesicular bodies (MVBs). Virus particles localized to MVBs approximately 1 hour after infection and affected the distribution of the organelle within cells. Interestingly, blocking Rab7 activity had no effect on association of the virus with MVBs. Productive virus infection depended on phosphatidylinositol 3-kinase (PI3K) activity, which meditates the formation of functional MVBs. Silencing Tsg101, Vps24, Vps4B, or Alix/Aip1, components of the endosomal sorting complex required for transport (ESCRT) pathway controlling MVB biogenesis, inhibited infection of wild-type virus as well as a novel pseudotyped vesicular stomatitis virus (VSV) bearing CCHFV glycoprotein, supporting a role for the MVB pathway in CCHFV entry. We further demonstrate that blocking transport out of MVBs still allowed virus entry while preventing vesicular acidification, required for membrane fusion, trapped virions in the MVBs. These findings suggest that MVBs are necessary for infection and are the sites of virus-endosome membrane fusion. Crimean-Congo hemorrhagic fever virus (CCHFV) is the cause of a severe, often fatal disease in humans. While it has been demonstrated that CCHFV cell entry depends on clathrin-mediated endocytosis, low pH, and early endosomes, the identity of the endosomes where virus penetrates into cell cytoplasm to initiate genome replication is unknown. Here, we showed that CCHFV was transported through early endosomes to multivesicular bodies (MVBs). We also showed that MVBs were likely the last organelle virus encountered before escaping into the cytoplasm. Our work has identified new cellular factors essential for CCHFV entry and potential novel targets for therapeutic intervention against this pathogen.
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影响因子：
64.8
作者：
Cote, Marceline;Misasi, John;Ren, Tao;Bruchez, Anna;Lee, Kyungae;Filone, Claire Marie;Hensley, Lisa;Li, Qi;Ory, Daniel;Chandran, Kartik;Cunningham, James
通讯作者：
Cunningham, James
影响因子：
3.3
作者：
Bishop, N;Woodmane, P
通讯作者：
Woodmane, P
影响因子：
5.4
作者：
Bergeron, Eric;Vincent, Martin J.;Nichol, Stuart T.
通讯作者：
Nichol, Stuart T.
DOI：
10.1083/jcb.131.6.1435
发表时间：
1995-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Feng Y;Press B;Wandinger-Ness A
通讯作者：
Wandinger-Ness A
影响因子：
4
作者：
Estrada-Pena, A.;Ruiz-Fons, F.;de la Fuente, J.
通讯作者：
de la Fuente, J.