Filovirus entry: a novelty in the viral fusion world.
Filovirus entry: a novelty in the viral fusion world.
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DOI：
10.3390/v4020258
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发表时间：
2012-02
期刊：
影响因子：
--
通讯作者：
Maury W
中科院分区：
文献类型：
--
作者：
Hunt CL;Lennemann NJ;Maury W
埃博拉病毒（EBOV）和马尔堡病毒（MARV）组成负链RNA病毒的丝状病毒家族，感染广泛的哺乳动物细胞。最近的研究表明，该病毒家族的细胞进入需要一系列细胞蛋白质相互作用和分子机制，其中一些是丝状病毒所特有的，另一些是所有病毒糖蛋白共同使用的。此处突出显示了此进入途径的详细信息。病毒进入细胞是由病毒糖蛋白1亚基（GP 1）与粘附因子和宿主细胞表面的一种或多种受体相互作用启动的。在上皮细胞上，我们最近证明TIM-1作为该病毒家族的受体，但其他细胞类型中的细胞表面受体仍未确定。在受体结合后，病毒主要通过巨胞饮内化到内体中，但也可能通过其他机制。在酸化的内体内，高度糖基化的GP 1被低pH依赖性细胞蛋白酶组织蛋白酶L和B切割成较小的形式，暴露受体结合位点（RBS）中的残基。GP 1的组织蛋白酶依赖性修剪后的分子事件的细节目前是不完整的;然而，处理的GP 1特异性地与含有尼曼匹克C1（NPC 1）蛋白的内体/溶酶体膜相互作用，并且NPC 1的表达是生产性感染所必需的，这表明GP/NPC 1相互作用可能是进入过程中的重要后期步骤。还可能需要额外的事件，例如进一步的GP 1加工和/或还原事件，以产生糖蛋白的融合就绪形式。一旦实现这一点，丝状病毒GP 2亚基中的序列通过与先前针对其他包膜病毒描述的机制类似的机制介导病毒/细胞膜融合。这种多步进入途径突出了丝状病毒独特的复杂和高度协调的内化和融合路径。
Ebolavirus (EBOV) and Marburgvirus (MARV) that compose the filovirus family of negative strand RNA viruses infect a broad range of mammalian cells. Recent studies indicate that cellular entry of this family of viruses requires a series of cellular protein interactions and molecular mechanisms, some of which are unique to filoviruses and others are commonly used by all viral glycoproteins. Details of this entry pathway are highlighted here. Virus entry into cells is initiated by the interaction of the viral glycoprotein1 subunit (GP1) with both adherence factors and one or more receptors on the surface of host cells. On epithelial cells, we recently demonstrated that TIM-1 serves as a receptor for this family of viruses, but the cell surface receptors in other cell types remain unidentified. Upon receptor binding, the virus is internalized into endosomes primarily via macropinocytosis, but perhaps by other mechanisms as well. Within the acidified endosome, the heavily glycosylated GP1 is cleaved to a smaller form by the low pH-dependent cellular proteases Cathepsin L and B, exposing residues in the receptor binding site (RBS). Details of the molecular events following cathepsin-dependent trimming of GP1 are currently incomplete; however, the processed GP1 specifically interacts with endosomal/lysosomal membranes that contain the Niemann Pick C1 (NPC1) protein and expression of NPC1 is required for productive infection, suggesting that GP/NPC1 interactions may be an important late step in the entry process. Additional events such as further GP1 processing and/or reducing events may also be required to generate a fusion-ready form of the glycoprotein. Once this has been achieved, sequences in the filovirus GP2 subunit mediate viral/cellular membrane fusion via mechanisms similar to those previously described for other enveloped viruses. This multi-step entry pathway highlights the complex and highly orchestrated path of internalization and fusion that appears unique for filoviruses.
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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：
5.4
作者：
Adam, B;Lins, L;Brasseur, R
通讯作者：
Brasseur, R
影响因子：
3.8
作者：
BECKER, S;SPIESS, M;KLENK, HD
通讯作者：
KLENK, HD
影响因子：
5.4
作者：
Dube, Derek;Brecher, Matthew B.;White, Judith M.
通讯作者：
White, Judith M.
影响因子：
6.4
作者：
Aleksandrowicz, Paulina;Marzi, Andrea;Schnittler, Hans-Joachim
通讯作者：
Schnittler, Hans-Joachim