Single Particle Imaging of Polarized Hepatoma Organoids upon Hepatitis C Virus Infection Reveals an Ordered and Sequential Entry Process.
Single Particle Imaging of Polarized Hepatoma Organoids upon Hepatitis C Virus Infection Reveals an Ordered and Sequential Entry Process.
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DOI：
10.1016/j.chom.2018.02.005
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发表时间：
2018-03-14
影响因子：
30.3
通讯作者：
Randall G
中科院分区：
文献类型：
--
作者：
Baktash Y;Madhav A;Coller KE;Randall G
丙型肝炎病毒（HCV）通过多种进入因子进入肝细胞，包括清道夫受体BI （SR-B1）、分化簇81 （CD81）、表皮生长因子受体（EGFR）、CLDN1 （CLDN1）和occludin （OCLN）。由于CLDN1和OCLN的紧密连接定位不易接近，HCV可能通过破坏细胞极性或迁移到紧密连接来接近它们。在这项研究中，我们成像HCV进入三维极化肝癌系统，并揭示病毒通过动作蛋白依赖机制顺序参与这些进入因子。HCV最初定位于基底外侧膜的早期进入因子SR-B1、CD81和EGFR，然后以动作蛋白依赖的方式在紧密连接处积累。HCV在紧密连接处与CLDN1和OCLN结合，并通过网格蛋白介导的内吞作用被内化，这是一个需要EGFR的活性过程。因此，HCV通过一个动态的、多步骤的过程参与并进入宿主细胞。HCV进入是复杂的，涉及多种宿主因素。Baktash等人通过荧光HCV病毒粒子成像极化肝癌类器官感染，确定了进入过程中的事件顺序。他们确定HCV病毒粒子与早期受体运输到紧密连接，然后以依赖egfr的方式内化。
Hepatitis C virus (HCV) enters hepatocytes via various entry factors, including scavenger receptor BI (SR-B1), cluster of differentiation 81 (CD81), epidermal growth factor receptor (EGFR), claudin-1 (CLDN1), and occludin (OCLN). As CLDN1 and OCLN are not readily accessible due to their tight junctional localization, HCV likely accesses them by either disrupting cellular polarity or migrating to the tight junction. In this study, we image HCV entry into a three-dimensional polarized hepatoma system and reveal that the virus sequentially engages these entry factors through actin-dependent mechanisms. HCV initially localizes with the early entry factors SR-B1, CD81, and EGFR at the basolateral membrane and then accumulates at the tight junction in an actin-dependent manner. HCV associates with CLDN1 and then OCLN at the tight junction and is internalized via clathrin-mediated endocytosis by an active process requiring EGFR. Thus, HCV uses a dynamic and multi-step process to engage and enter host cells. HCV entry is complex and involves multiple host factors. By imaging the infection of polarized hepatoma organoids with fluorescent HCV virions, Baktash et al. define the sequence of events during entry. They determine that HCV virions traffic with early receptors to tight junctions and then internalize in an EGFR-dependent manner.
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影响因子：
6.7
作者：
Coller KE;Berger KL;Heaton NS;Cooper JD;Yoon R;Randall G
通讯作者：
Randall G
影响因子：
4.8
作者：
Bartosch, B;Vitelli, A;Cosset, FL
通讯作者：
Cosset, FL
影响因子：
8.8
作者：
Gerold G;Meissner F;Bruening J;Welsch K;Perin PM;Baumert TF;Vondran FW;Kaderali L;Marcotrigiano J;Khan AG;Mann M;Rice CM;Pietschmann T
通讯作者：
Pietschmann T
DOI：
10.1073/pnas.1004618107
发表时间：
2010-05-18
影响因子：
11.1
作者：
Mercer, Jason;Knebel, Stephan;Helenius, Ari
通讯作者：
Helenius, Ari
影响因子：
4.8
作者：
Barth, H;Schäfer, C;Baumert, TF
通讯作者：
Baumert, TF