PolyC-binding protein 1 interacts with 5'-untranslated region of enterovirus 71 RNA in membrane-associated complex to facilitate viral replication.
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.
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
Zhen
Z
Luo
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
Xingchen
X
Dong
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
Youxing
Y
Li
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
Qi
Q
Zhang
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
Cholho
C
Kim
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
Yu
Y
Song
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
Lei
L
Kang
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
Yingle
Y
Liu
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, Hubei, China.
Kailang
K
Wu
State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, Hubei, China ; Chinese-French Liver Disease Research Institute, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China.
Jianguo
J
Wu
D020121:5' Untranslated Regions; D000595:Amino Acid Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000821:virology; D029821:Enterovirus A, Human / Q000235:genetics*; D006367:HeLa Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D055029:Inverted Repeat Sequences; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins; D014779:Virus Replication
D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; C094604:PCBP1 protein, human; D012367:RNA, Viral; D016601:RNA-Binding Proteins