PolyC-binding protein 1 interacts with 5'-untranslated region of enterovirus 71 RNA in membrane-associated complex to facilitate viral replication

• Published in: PloS one 2014-01, Vol.9 (1), p.e87491-e87491
• Main Authors: Luo, Zhen, Dong, Xingchen, Li, Youxing, Zhang, Qi, Kim, Cholho, Song, Yu, Kang, Lei, Liu, Yingle, Wu, Kailang, Wu, Jianguo
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; 5' Untranslated Regions; Amino Acid Sequence; Binding Sites; Biology; Cellular proteins; Children; Coxsackievirus infections; Cytoplasm; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - virology; Enterovirus; Enterovirus A, Human - genetics; Enteroviruses; Gene expression; Genomes; Genomics; Hand-foot-and-mouth disease; Health aspects; HeLa Cells; Hepatitis; Heterogeneous-Nuclear Ribonucleoproteins - metabolism; Homology; Humans; Infections; Intracellular Membranes - metabolism; Inverted Repeat Sequences; Laboratories; Life sciences; Localization; Medicine; Membranes; Molecular Sequence Data; Mortality; Nervous system diseases; Neurological diseases; Nuclei (cytology); Poly(C)-binding protein; Protein Binding; Protein Structure, Tertiary; Protein Transport; Proteins; Replication; Ribonucleic acid; RNA; RNA, Viral - genetics; RNA, Viral - metabolism; Viral infections; Viral proteins; Virology; Virus Replication; Viruses; West Nile virus
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0087491

Enterovirus 71 (EV71) is one causative agent of hand, foot, and mouth disease (HFMD), which may lead to severe neurological disorders and mortality in children. EV71 genome is a positive single-stranded RNA containing a single open reading frame (ORF) flanked by 5'-untranslated region (5'UTR) and 3'UTR. The 5'UTR is fundamentally important for virus replication by interacting with cellular proteins. Here, we revealed that poly(C)-binding protein 1 (PCBP1) specifically binds to the 5'UTR of EV71. Detailed studies indicated that the RNA-binding K-homologous 1 (KH1) domain of PCBP1 is responsible for its binding to the stem-loop I and IV of EV71 5'UTR. Interestingly, we revealed that PCBP1 is distributed in the nucleus and cytoplasm of uninfected cells, but mainly localized in the cytoplasm of EV71-infected cells due to interaction and co-localization with the viral RNA. Furthermore, sub-cellular distribution analysis showed that PCBP1 is located in ER-derived membrane, in where virus replication occurred in the cytoplasm of EV71-infected cells, suggesting PCBP1 is recruited in a membrane-associated replication complex. In addition, we found that the binding of PCBP1 to 5'UTR resulted in enhancing EV71 viral protein expression and virus production so as to facilitate viral replication. Thus, we revealed a novel mechanism in which PCBP1 as a positive regulator involved in regulation of EV71 replication in the host specialized membrane-associated replication complex, which provides an insight into cellular factors involved in EV71 replication.