Cytomegalovirus Downregulates IRE1 to Repress the Unfolded Protein Response

摘要: During viral infection, a massive demand for glycoproteins can overwhelm the capacity of protein folding and quality control machinery, leading to an accumulation unfolded proteins in endoplasmic reticulum (ER). To restore ER homeostasis, cells initiate response (UPR) by activating three ER-to-nucleus signaling pathways, which inositol-requiring enzyme 1 (IRE1)-dependent pathway is most conserved. reduce stress, UPR decreases synthesis, increases degradation proteins, upregulates chaperone expression enhance folding. Cytomegaloviruses, as other pathogens, modulate their own advantage. However, molecular mechanisms responsible modulation remained be identified. In this study, we investigated IRE1 murine cytomegalovirus (MCMV) found that IRE1-mediated mRNA splicing X-box binding (XBP1) repressed infected cells. By affinity purification, identified M50 IRE1-interacting protein. transfected or MCMV-infected induced substantial downregulation levels. The N-terminal conserved region was required interaction with IRE1. Moreover, UL50, human (HCMV) homolog M50, affected same way. Thus concluded represents previously undescribed strategy curb UPR.