| Summary: | 碩士 === 長庚大學 === 基礎醫學研究所 === 94 === Accumulation of unfolded or misfolded proteins in the ER (i.e. ER stress) triggers the unfolded protein response (UPR), a cellular adaptive response that functions to maintain ER homeostasis and cell survival. UPR activation leads to the inhibition of protein translation through phosphorylation of the a-subunit of the eukaryotic translation initiation factor eIF2 (eIF2a). In addition, the combined activation of two other transmembrane ER stress sensors, ATF6 and IRE1 initiates signaling cascades, leading to the transcription of ER chaperones. Enterovirus 71 (EV71) is a non-enveloped, positive single stranded RNA genome virus and belongs to Enterovirus genus within Picornaviridae. Poliovirus, a related to EV71 and its infection affected host protein transport from ER to Golgi and thus may cause accumulation of host protein in the ER. The aim of the present study was to determine whether infection of EV71 in RD cells could activate UPR and resulted in altered viral replication. We have demonstrated that EV71-infection induced phosphorylation of eIF2a, over-expression of ER chaperone proteins, suppressed global protein synthesis, and IRE1-mediated induction of XBP1(S) mRNA. In contrast to ER stress inducers, DTT and thapsigargin, UPR activated by EV71 up-regulates chaperones at protein level. We also demonstrated that viral protein synthesis was reduced under an ER stress environment and the quantity of viral mRNA was rescued in EV71 infected Grp78/BiP over-expressing RD cells. Collectively, these results indicate that UPR caused by EV71 is a host defense mechanism.
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