Cleavage activation of respiratory viruses – Half a century of history from Sendai virus to SARS-CoV-2

抄録

For many viruses, cleavage activation of membrane fusion protein by host proteases is required for infection. This knowledge is based on the historical studies on Sendai virus in the 1970s. From the 1970s to the 1990s, the avian influenza virus and Newcastle disease virus were studied, showing a clear link between virulence and host proteases' cleavage activation of viral membrane fusion proteins (hemagglutinin and fusion proteins). In these viruses, the 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 membrane fusion proteins of various respiratory viruses, including seasonal influenza viruses, was demonstrated. In late 2019, SARS-CoV-2 emerged and caused a pandemic. This virus continues to mutate, producing variants that cause a global pandemic. The spike protein of SARS-CoV-2 is characterized by two cleavage sites, each undergoing cleavage by furin and TMPRSS2 to achieve membrane fusion activity. SARS-CoV-2 variants show altered sensitivity to these proteases. Thus, studying the cleavage activation of the membrane fusion protein by host proteases is still critical to understanding the ongoing pandemic and developing countermeasures against it.