Chao Sun, Mengmeng Liu, Jitao Chang, Decheng Yang, Bo Zhao, Haiwei Wang, Guohui Zhou, Changjiang Weng, Li Yu
J Virol. 2020 Mar 11. pii: JVI.00282-20. doi: 10.1128/JVI.00282-20. [Epub ahead of print]
Upon infection, the highly structured 5' untranslated region (5'UTR) of picornavirus is involved in viral protein translation and RNA synthesis. As a critical element in the 5'UTR, the internal ribosome entry site (IRES) binds to various cellular proteins to function in these processes of picornavirus replication. Foot-and-mouth disease virus (FMDV) is an important member in the family Picornaviridae, and its 5'UTR contains a functional IRES element. In this study, the cellular heterogeneous nuclear ribonucleoprotein L (hnRNP L) was identified as an IRES-binding protein for FMDV by using biotinylated RNA pulldown assay, mass spectrometry (MS) analysis and determination of hnRNP L-IRES interaction regions. Further, we found that the hnRNP L inhibited the growth of FMDV through binding to the viral IRES, and the inhibitory effect of hnRNP L on FMDV growth was produced not by affecting FMDV IRES-mediated translation but by influencing viral RNA synthesis. Finally, hnRNP L was demonstrated to coimmunoprecipitate with 3Dpol in a FMDV RNA-dependent manner in the infected cells. Thus, our results suggest that hnRNP L, as a critical IRES-binding protein, negatively regulates FMDV replication by inhibiting viral RNA synthesis and possibly staying in the replication complex.IMPORTANCEPicornaviruses, as a large family of human and animal pathogens, cause a bewildering array of disease syndromes. Many host factors are implicated in the pathogenesis of these viruses, and some proteins interact with the viral IRES elements to function. Here, we report for the first time that cellular hnRNP L specifically interacts with the IRES of the picornavirus FMDV and negatively regulates FMDV replication through inhibiting viral RNA synthesis. Furthermore, our results showed that hnRNP L coimmunoprecipitates with FMDV 3Dpol in a viral RNA-dependent manner, suggesting that it may be present in the replication complex to function. The data presented here would facilitate a further understanding of virus-host interactions and the pathogenesis of picornavirus infections.
Copyright © 2020 American Society for Microbiology.