Role of host factors in SARS-CoV-2 entry.

Role of host factors in SARS-CoV-2 entry.
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DOI:
10.1016/j.jbc.2021.100847
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发表时间:
2021-07
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
Liu SL
Liu SL
中科院分区:
其他
文献类型:
--
作者:
Evans JP;Liu SL

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目前的SARS-CoV-2大流行突出了高致病性冠状病毒在人类中的人畜共患传播是一个紧迫的关切。最近的工作有助于阐明SARS-CoV-2进入细胞的机制,它决定了宿主和组织的特异性趋向性、致病性和人畜共患传播。在这里,我们讨论关于影响SARS-CoV-2进入的因素的最新发现。我们首先综述了病毒刺突蛋白(S)的主要特征,它通过与SARS-CoV-2受体血管紧张素转换酶2结合来介导病毒包膜和宿主细胞膜的融合。然后我们研究了宿主蛋白包括跨膜蛋白酶丝氨酸2和组织蛋白在处理S进入病毒过程中的作用,以及这种处理对内体和质膜病毒进入途径的影响。我们进一步讨论了几个促进SARS-CoV-2进入的宿主辅助因子的最新工作,包括Neuropilin-1,CD147,磷脂酰丝氨酸受体,硫酸乙酰肝素蛋白多糖,唾液酸和C型凝集素。最后,我们讨论了干扰SARS-CoV-2入侵的两个关键宿主限制因素,即干扰素诱导的跨膜蛋白和淋巴细胞抗原6复合体E。SARS-CoV-2的特征是在其他人类冠状病毒的背景下介绍的,突出了独特的方面。此外,我们确定了对SARS-CoV-2进入的理解上的差距,这些差距将需要未来的研究来解决。
The zoonotic transmission of highly pathogenic coronaviruses into the human population is a pressing concern highlighted by the ongoing SARS-CoV-2 pandemic. Recent work has helped to illuminate much about the mechanisms of SARS-CoV-2 entry into the cell, which determines host- and tissue-specific tropism, pathogenicity, and zoonotic transmission. Here we discuss current findings on the factors governing SARS-CoV-2 entry. We first reviewed key features of the viral spike protein (S) mediating fusion of the viral envelope and host cell membrane through binding to the SARS-CoV-2 receptor, angiotensin-converting enzyme 2. We then examined the roles of host proteases including transmembrane protease serine 2 and cathepsins in processing S for virus entry and the impact of this processing on endosomal and plasma membrane virus entry routes. We further discussed recent work on several host cofactors that enhance SARS-CoV-2 entry including Neuropilin-1, CD147, phosphatidylserine receptors, heparan sulfate proteoglycans, sialic acids, and C-type lectins. Finally, we discussed two key host restriction factors, i.e., interferon-induced transmembrane proteins and lymphocyte antigen 6 complex locus E, which can disrupt SARS-CoV-2 entry. The features of SARS-CoV-2 are presented in the context of other human coronaviruses, highlighting unique aspects. In addition, we identify the gaps in understanding of SARS-CoV-2 entry that will need to be addressed by future studies.
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