The nonstructural proteins of PEDV
The translated products poly-proteins pp1a and pp1ab of the ORF1a and
ORF1b transcripts are cleaved into 16 mature replicase proteins
nsp1-nsp16 per the action of the Papain -like protease (PLpro is encoded
by nsp3) and 3C like protease (EJ et al., 2003; T. V et al., 2003).
Previous study indicated that the nsp1 protein has the most pronounced
effect on the host innate immune response among all encoded proteins of
PEDV. Furthermore, the action mechanism of it is mediated by the
degradation of transcription factor binding protein (CREB-binding
protein, CBP) and inhibition of interferon (IFN) stimulated gene (IFN
stimulated genes, ISGs) expression to suppress the expression of IFN-β,
as markedly different from other proteins with interferon antagonistic
activity (Q, K, & D, 2016). Meanwhile, the nsp1 is a potential
virulence factor and a target for vaccine development since it can
disrupt host gene expression and stimulate an antiviral response,
thereby blunting the innate immune response of the host to the
coronavirus pathogens (N. K, SI, KG, & S, 2015). The nsp5 protein, also
called 3CLpro, functions to split proproteins between the nsp5 and
nsp16, thus turning them into mature proteins which participate in
various stages of virus replication (T. S et al., 2015). The functional
experiments on the nsp5 also revealed that it plays an antagonistic role
of interferon through shearing NEMO (NF-κB essential modulator),
moreover, the cystine protease activity at the catalytic site of the
nsp5 is a key factor for achieving this through cleaving Gln231 in the
NEMO protein (Wang D, L, Y, et al., 2016). Likewise, intensive studies
on the nsp9 of PEDV suggested that it may also play a vital role in
virus replication in the form of homodimers, as similar to those of
SARS-CoV and MERS-CoV (S. G et al., 2004). Moreover, other study has
also demonstrated the presence of different dimerized forms of the nsp9
protein, which may enhance its nucleic acid binding affinity (Z. Z et
al., 2018). Since no or few studies addressing the roles of other PEDV
non-structural proteins in terms of viral infection are present and
further investigations on these initially characterized ones are
required, these should be the future emphases.