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.