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.