Enterovirus 71 protease 2Apro and 3Cpro differentially inhibit the cellular endoplasmic reticulum-associated degradation (ERAD) pathway via distinct mechanisms, and enterovirus 71 hijacks ERAD component p97 to promote its replication.

ABSTRACT: Endoplasmic reticulum-associated degradation (ERAD) is an important function for cellular homeostasis. The mechanism of how picornavirus infection interferes with ERAD remains unclear. In this study, we demonstrated that enterovirus 71 (EV71) infection significantly inhibits cellular ERAD by targeting multiple key ERAD molecules with its proteases 2Apro and 3Cpro using different mechanisms. Ubc6e was identified as the key E2 ubiquitin-conjugating enzyme in EV71 disturbed ERAD. EV71 3Cpro cleaves Ubc6e at Q219G, Q260S, and Q273G. EV71 2Apro mainly inhibits the de novo synthesis of key ERAD molecules Herp and VIMP at the protein translational level. Herp differentially participates in the degradation of different glycosylated ERAD substrates α-1 antitrypsin Null Hong Kong (NHK) and the C-ter

SUBMITTER: Wang T 

PROVIDER: S-EPMC5650186 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature