Type Ⅱ transmembrane serine proteases (TTSPs)
TTSPs being a family with more than 20 members can be mainly divided into four subgroups: HAT/DESC, hepsin/TMPRSS, matriptase and corin (S. R & TH, 2008). TTSPs consisting of several functional domains are expressed in many tissues and cell mucosal epithelia, moreover, the localization of them in respiratory mucosal epithelium often facilitates respiratory virus infection (B.-F. E et al., 2010). This role of TTSPs is closely associated with the protease activity of them. Intriguingly, the serine protease inhibitor ABESF-HCl could significantly inhibit the replication of PEDV in Vero cells (JE, DJ, & HJ, 2014). Furthermore, the culture of PEDV could be achieved in stably transmembrane protease serine 2 (TMPRSS2) expressing Vero cells even in the absence of trypsin. Meanwhile, indirect immunofluorescence revealed TMPRSS2-induced cell fusion in virus-infected cells (S. K, S, M, & F, 2011). Likewise, similar role for mosaic serine protease large-form (MSPL) in enhancing the in vitro proliferation of PEDV has been described (S. W et al., 2017). These suggest that like trypsin, the promoting effect of TMPRSS2 and MSPL on PEDV proliferation may be ascribed to their ability of catalyzing the cleavage of the S protein, thus enhancing the entry and release of viral particles during PEDV infection. Additionally, Dipeptidyl Peptidase 4 (DPP4), also called CD26 with the activity of protease and the wide distribution in many tissues and cells, is very conserved among various species and play an important role in the infection of Middle East Respiratory Syndrome virus and other emerging human coronaviruses (O. K et al., 2013). Though robust evidence remains to be provided, CRISPR/Cas9 technology-mediated ablation of CD26/DPP4 gene in target cells should help to illustrate this issue.