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Enterovirus 71 induces dsRNA/PKR-dependent cytoplasmic redistribution of GRP78/BiP to promote viral replication.
Jheng, Jia-Rong; Wang, Shin-Chyang; Jheng, Chao-Rih; Horng, Jim-Tong.
Afiliação
  • Jheng JR; Graduate Institute of Biomedical Sciences and Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
  • Wang SC; Graduate Institute of Biomedical Sciences and Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
  • Jheng CR; Graduate Institute of Biomedical Sciences and Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
  • Horng JT; Graduate Institute of Biomedical Sciences and Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Emerg Microbes Infect ; 5: e23, 2016 Mar 23.
Article em En | MEDLINE | ID: mdl-27004760
ABSTRACT
GRP78/BiP is an endoplasmic reticulum (ER) chaperone protein with the important function of maintaining ER homeostasis, and the overexpression of GRP78/BiP alleviates ER stress. Our previous studies showed that infection with enterovirus 71 (EV71), a (+)RNA picornavirus, induced GRP78/BiP upregulation; however, ectopic GRP78/BiP overexpression in ER downregulates virus replication and viral particle formation. The fact that a virus infection increases GRP78/BiP expression, which is unfavorable for virus replication, is counterintuitive. In this study, we found that the GRP78/BiP protein level was elevated in the cytoplasm instead of in the ER in EV71-infected cells. Cells transfected with polyinosinic-polycytidylic acid, a synthetic analog of replicative double-stranded RNA (dsRNA), but not with viral proteins, also exhibited upregulation and elevation of GRP78/BiP in the cytosol. Our results further demonstrate that EV71 infections induce the dsRNA/protein kinase R-dependent cytosolic accumulation of GRP78/BiP. The overexpression of a GRP78/BiP mutant lacking a KDEL retention signal failed to inhibit both dithiothreitol-induced eIF2α phosphorylation and viral replication in the context of viral protein synthesis and viral titers. These data revealed that EV71 infection might cause upregulation and aberrant redistribution of GRP78/BiP to the cytosol, thereby facilitating virus replication.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Replicação Viral / RNA de Cadeia Dupla / Enterovirus Humano A / Citoplasma / Proteínas de Choque Térmico Limite: Humans Idioma: En Revista: Emerg Microbes Infect Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Taiwan

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Replicação Viral / RNA de Cadeia Dupla / Enterovirus Humano A / Citoplasma / Proteínas de Choque Térmico Limite: Humans Idioma: En Revista: Emerg Microbes Infect Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Taiwan