Abstract:
Many viruses require the cleavage-activation of membrane fusion proteins by host proteases in the course of infection. This knowledge is based on historical studies of Sendai virus in the 1970s. From the 1970s to the 1990s, avian influenza virus and Newcastle disease virus were studied, showing a clear link between virulence and the cleavage-activation of viral membrane fusion proteins (hemagglutinin and fusion proteins) by host proteases. In these viruses, cleavage of viral membrane fusion proteins by furin is the basis for their high virulence. Subsequently, from the 2000s to the 2010s, the importance of TMPRSS2 in activating the membrane fusion proteins of various respiratory viruses, including seasonal influenza viruses, was demonstrated. In late 2019, severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) emerged and caused a pandemic. The virus continues to mutate, producing variants that have caused global pandemics. The spike protein of SARS-CoV-2 is characterized by two cleavage sites, each of which is cleaved by furin and TMPRSS2 to achieve membrane fusion. SARS-CoV-2 variants exhibit altered sensitivity to these proteases. Thus, studying the cleavage-activation of membrane fusion proteins by host proteases is critical for understanding the ongoing pandemic and developing countermeasures against it.
摘要:
对于许多病毒来说,感染需要通过宿主蛋白酶裂解激活膜融合蛋白。这些知识是基于1970年代对仙台病毒的历史研究。从1970年代到1990年代,研究了禽流感病毒和新城疫病毒,显示病毒膜融合蛋白(血凝素和融合蛋白)的毒力和宿主蛋白酶裂解活化之间的明确联系。在这些病毒中,弗林蛋白酶对病毒膜融合蛋白的切割是其高毒力的基础。随后,从2000年代到2010年代,TMPRSS2在激活各种呼吸道病毒的膜融合蛋白中的重要性,包括季节性流感病毒,被证明了。2019年底,SARS-CoV-2出现并引起了大流行。这种病毒继续变异,产生导致全球大流行的变体。SARS-CoV-2的刺突蛋白具有两个切割位点,每个都经历弗林蛋白酶和TMPRSS2的切割以实现膜融合活性。SARS-CoV-2变体显示对这些蛋白酶的敏感性改变。因此,研究宿主蛋白酶对膜融合蛋白的裂解激活对于了解正在进行的大流行和制定对策仍然至关重要。