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Heterogeneous nuclear ribonuclear protein K interacts with the enterovirus 71 5' untranslated region and participates in virus replication

¹ Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan, ROC
² Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan, ROC
³ Graduate Program in Biomedical Science, Chang Gung University, Taoyuan, Taiwan, ROC
⁴ Department of Molecular Genetics, Microbiology and Immunology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ, USA

Correspondence
Shin-Ru Shih
srshih{at}mail.cgu.edu.tw

Enterovirus 71 (EV71) is a picornavirus that can cause severe neurological complications in children. Like other picornaviruses, the genomic RNA of EV71 contains a long 5' untranslated region (UTR). Cellular proteins interact with the EV71 5' UTR, and these interactions are important for virus replication. Using an RNA pull-down assay and proteomics approaches, this study identified the heterogeneous nuclear ribonucleoprotein K (hnRNP K) as one of the EV71 5' UTR-associated proteins. The interaction between hnRNP K and the 5' UTR was further confirmed by mapping the interaction regions to stem–loops I–II and IV in the 5' UTR. During EV71 infection, hnRNP K was enriched in the cytoplasm where virus replication occurs, whereas hnRNP K was localized in the nucleus in mock-infected cells. Viral yields were found to be significantly lower in hnRNP K knockdown cells and viral RNA synthesis was delayed in hnRNP K knockdown cells in comparison with negative-control cells treated with small interfering RNA. These results suggest that hnRNP K interacts with the EV71 5' UTR and participates in virus replication.

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