Regulation of IRE1-XBP1 Pathway of Unfolded Protein Response by Enterovirus 71

• Main Authors: Chiou Yan Lin, 林秋艷
• Other Authors: J. T. Horng
• Format: Others
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/62811582479750186966

碩士 === 長庚大學 === 生物醫學研究所 === 98 === Enoplasmic reticulum (ER) is the principal site for folding and maturation of transmembrane, secretory and ER-resident proteins. When accumulation of unfolded proteins in the ER, ER stress is induced. To cope with the stress, cells activate an intracellular signaling pathway - the unfolded protein response (UPR). Our laboratory has revealed that the UPR pathway can be triggered by enterovirus71 (EV71). Interestingly, inositol-requiring protein-1 (IRE1) was activated after EV71 BrCr strain infection, but the splicing form of XBP1 (XBP1(S)) protein was not increased. Besides, XBP1(S) protein level was not affected when rhabdomyosarcoma cells were infected with UV-inactivated virus. The decrease of was possibly due to expression of EV71 viral RNA or viral proteins. XBP1(S) protein was not only deceased under poly(I:C) transfection but also under EV71 2A protein expression. We further provided evidence that cleavage of eukaryotic translation initiation factor 4G (eIF4G) by EV71 2A protein resulted in the decrease of XBP1(S) protein. On the other hand, we also investigated the effect of XBP1(S) protein on EV71.We found overexpression of XBP1(S) inhibited the synthesis of EV71 viral protein and viral RNA and reduced the production of EV71 viral particles. We further demonstrated that the derease of EV71 viral protein resulted from XBP1(S) overexpression rather than due to the effect of EV71 IRES-dependent translational shutoff.