The Hypervariable Amino-Terminus of P1 Protease Modulates Potyviral Replication and Host Defense Responses

The replication of many rna viruses involves the translation of polyproteins,whose processing by endopeptidases is a critical step for the release of functional subunits. p1 is the first protease encoded in plant potyvirus genomes; once activated by an as-yet-unknown host factor,it acts in cis on its own c-terminal end,hydrolyzing the p1-hcpro junction. earlier research suggests that p1 cooperates with hcpro to inhibit host rna silencing defenses. using plum pox virus as a model,we show that although p1 does not have a major direct role in rna silencing suppression,it can indeed modulate hcpro function by its self-cleavage activity. to study p1 protease regulation,we used bioinformatic analysis and in vitro activity experiments to map the core c-terminal catalytic domain. we present evidence that the hypervariable region that precedes the protease domain is predicted as intrinsically disordered,and that it behaves as a negative regulator of p1 proteolytic activity in in vitro cleavage assays. in viral infections,removal of the p1 protease antagonistic regulator is associated with greater symptom severity,induction of salicylate-dependent pathogenesis-related proteins,and reduced viral loads. we suggest that fine modulation of a viral protease activity has evolved to keep viral amplification below host-detrimental levels,and thus to maintain higher long-term replicative capacity. © 2014 pasin et al.