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Volume 37 Issue 5
October 2022
    Citation: Ziyu Chen, Xiaobei Xiong, Yiyang Li, Muhan Huang, Yujie Ren, Di Wu, Yang Qiu, Mingzhou Chen, Ting Shu, Xi Zhou. The nonstructural protein 2C of Coxsackie B virus has RNA helicase and chaperoning activities .VIROLOGICA SINICA, 2022, 37(5) : 656-663.  http://dx.doi.org/10.1016/j.virs.2022.05.004
    shu

    The nonstructural protein 2C of Coxsackie B virus has RNA helicase and chaperoning activities

    • a State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China;

    • b State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China;

    • c University of Chinese Academy of Sciences, Beijing, 100081, China

    • RNA-remodeling proteins, including RNA helicases and chaperones, play vital roles in the remodeling of structured RNAs. During viral replication, viruses require RNA-remodeling proteins to facilitate proper folding and/or re-folding the viral RNA elements. Coxsackieviruses B3 (CVB3) and Coxsackieviruses B5 (CVB5), belonging to the genus Enterovirus in the family Picornaviridae, have been reported to cause various infectious diseases such as hand-foot-and-mouth disease, aseptic meningitis, and viral myocarditis. However, little is known about whether CVB3 and CVB5 encode any RNA remodeling proteins. In this study, we showed that 2C proteins of CVB3 and CVB5 contained the conserved SF3 helicase A, B, and C motifs, and functioned not only as RNA helicase that unwound RNA helix bidirectionally in an NTP-dependent manner, but also as RNA chaperone that remodeled structured RNAs and facilitated RNA strand annealing independently of NTP. In addition, we determined that the NTPase activity and RNA helicase activity of 2C proteins of CVB3 and CVB5 were dependent on the presence of divalent metallic ions. Our findings demonstrate that 2C proteins of CVBs possess RNA-remodeling activity and underline the functional importance of 2C protein in the life cycle of CVBs.
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      1. Babb, J.M., Stoneman, M.E., Stern, H., 1961. Myocarditis and croup caused by Coxsackie virus type B5. Arch. Dis. Child. 36, 551-556.

      2. Bleichert, F., Baserga, S.J., 2007. The long unwinding road of RNA helicases. Mol. Cell. 27, 339-352.

      3. Caruthers, J.M., McKay, D.B., 2002. Helicase structure and mechanism. Curr. Opin.Struct. Biol. 12, 123-133.

      4. Crowell, R.L., Landau, B.J., 1997. A short history and introductory background on the coxsackieviruses of group B. Curr. Top. Microbiol. Immunol. 223, 1-11.

      5. Fang, Y., Wang, C., Wang, C., Yang, R., Bai, P., Zhang, X.-Y., Kong, J., Yin, L., Qiu, Y., Zhou, X., 2021. Antiviral peptides targeting the helicase activity of enterovirus nonstructural protein 2C. J. Virol. 95 e02324-02320.

      6. Gao, F., Bian, L., Hao, X., Hu, Y., Yao, X., Sun, S., Chen, P., Yang, C., Du, R., Li, J., Zhu, F., Mao, Q., Liang, Z., 2018. Seroepidemiology of coxsackievirus B5 in infants and children in Jiangsu province, China. Hum. Vaccines Immunother. 14, 74-80.

      7. Gebhard, L.G., Kaufman, S.B., Gamarnik, A.V., 2012. Novel ATP-independent RNA annealing activity of the dengue virus NS3 helicase. PLoS One 7, e36244.

      8. Gorbalenya, A.E., Koonin, E.V., 1993. Helicases:amino acid sequence comparisons and structure-function relationships. Curr. Opin. Struct. Biol. 3, 419-429.

      9. Han, Z., Zhang, Y., Huang, K., Wang, J., Tian, H., Song, Y., Yang, Q., Yan, D., Zhu, S., Yao, M., Wang, X., Xu, W., 2019. Two Coxsackievirus B3 outbreaks associated with hand, foot, and mouth disease in China and the evolutionary history worldwide. BMC Infect. Dis. 19, 466.

      10. Jarmoskaite, I., Russell, R., 2014. RNA helicase proteins as chaperones and remodelers.Annu. Rev. Biochem. 83, 697-725.

      11. Lee, S.T., Ki, C.S., Lee, N.Y., 2007. Molecular characterization of enteroviruses isolated from patients with aseptic meningitis in Korea, 2005. Arch. Virol. 152, 963-970.

      12. Li, T.F., Hosmillo, M., Schwanke, H., Shu, T., Wang, Z., Yin, L., Curry, S., Goodfellow, I.G., Zhou, X., 2018. Human norovirus NS3 has RNA helicase and chaperoning activities.J. Virol. 92, e01606-e01617.

      13. Lin, B.Y., Makhov, A.M., Griffith, J.D., Broker, T.R., Chow, L.T., 2002. Chaperone proteins abrogate inhibition of the human papillomavirus (HPV) E1 replicative helicase by the HPV E2 protein. Mol. Cell Biol. 22, 6592-6604.

      14. Musier-Forsyth, K., 2010. RNA remodeling by chaperones and helicases. RNA Biol. 7, 632-633.

      15. Pond, K., World Health Organization, Water, S., Health, T., 2005. Water Recreation and Disease:Plausibility of Associated Infections:Acute Effects, Sequelae and Mortality.World Health Organization, Geneva, pp. 199-207.

      16. Russell, R., 2008. RNA misfolding and the action of chaperones. Front. Biosci. 13, 1-20.

      17. Shu, T., Gan, T., Bai, P., Wang, X., Qian, Q., Zhou, H., Cheng, Q., Qiu, Y., Yin, L., Zhong, J., Zhou, X., 2019. Ebola virus VP35 has novel NTPase and helicase-like activities. Nucleic Acids Res. 47, 5837-5851.

      18. Shu, T., Huang, M., Wu, D., Ren, Y., Zhang, X., Han, Y., Mu, J., Wang, R., Qiu, Y., Zhang, D.Y., Zhou, X., 2020. SARS-Coronavirus-2 Nsp13 possesses NTPase and RNA helicase activities that can Be inhibited by bismuth salts. Virol. Sin. 35, 321-329.

      19. Singleton, M., Dillingham, M., Wigley, D., 2007. Structure and mechanism of helicases and nucleic acid translocases. Annu. Rev. Biochem. 76, 23-50.

      20. Tao, Z., Song, Y., Li, Y., Liu, Y., Jiang, P., Lin, X., Liu, G., Song, L., Wang, H., Xu, A., 2012. Coxsackievirus B3, shandong province, China, 1990-2010. Emerg. Infect. Dis. 18, 1865-1867.

      21. Wang, Q., Han, Y., Qiu, Y., Zhang, S., Tang, F., Wang, Y., Zhang, J., Hu, Y., Zhou, X., 2012. Identification and characterization of RNA duplex unwinding and ATPase activities of an alphatetravirus superfamily 1 helicase. Virology 433, 440-448.

      22. Wong, A.H., Lau, C.S., Cheng, P.K., Ng, A.Y., Lim, W.W., 2011. Coxsackievirus B3-associated aseptic meningitis:an emerging infection in Hong Kong. J. Med. Virol. 83, 483-489.

      23. Xia, H., Wang, P., Wang, G.C., Yang, J., Sun, X., Wu, W., Qiu, Y., Shu, T., Zhao, X., Yin, L., Qin, C.F., Hu, Y., Zhou, X., 2015. Human enterovirus nonstructural protein 2CATPase functions as both an RNA helicase and ATP-independent RNA chaperone. PLoS Pathog. 11, e1005067.

      24. Zhang, H., Morgan-Capner, P., Latif, N., Pandolfino, Y.A., Fan, W., Dunn, M.J., Archard, L.C., 1997. Coxsackievirus B3-induced myocarditis. Characterization of stable attenuated variants that protect against infection with the cardiovirulent wildtype strain. Am. J. Pathol. 150, 2197-2207.

      25. Zhang, W., Lin, X., Jiang, P., Tao, Z., Liu, X., Ji, F., Wang, T., Wang, S., Lv, H., Xu, A., Wang, H., 2016. Complete genome sequence of a coxsackievirus B3 recombinant isolated from an aseptic meningitis outbreak in eastern China. Arch. Virol. 161, 2335-2342.

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      The nonstructural protein 2C of Coxsackie B virus has RNA helicase and chaperoning activities

        Corresponding author: Mingzhou Chen, chenmz@whu.edu.cn
        Corresponding author: Ting Shu, shuting@wh.iov.cn
        Corresponding author: Xi Zhou, zhouxi@wh.iov.cn
      • a State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China;
      • b State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China;
      • c University of Chinese Academy of Sciences, Beijing, 100081, China
      • Received Date: 30 March 2022
      • Accepted Date: 10 May 2022

      Abstract: RNA-remodeling proteins, including RNA helicases and chaperones, play vital roles in the remodeling of structured RNAs. During viral replication, viruses require RNA-remodeling proteins to facilitate proper folding and/or re-folding the viral RNA elements. Coxsackieviruses B3 (CVB3) and Coxsackieviruses B5 (CVB5), belonging to the genus Enterovirus in the family Picornaviridae, have been reported to cause various infectious diseases such as hand-foot-and-mouth disease, aseptic meningitis, and viral myocarditis. However, little is known about whether CVB3 and CVB5 encode any RNA remodeling proteins. In this study, we showed that 2C proteins of CVB3 and CVB5 contained the conserved SF3 helicase A, B, and C motifs, and functioned not only as RNA helicase that unwound RNA helix bidirectionally in an NTP-dependent manner, but also as RNA chaperone that remodeled structured RNAs and facilitated RNA strand annealing independently of NTP. In addition, we determined that the NTPase activity and RNA helicase activity of 2C proteins of CVB3 and CVB5 were dependent on the presence of divalent metallic ions. Our findings demonstrate that 2C proteins of CVBs possess RNA-remodeling activity and underline the functional importance of 2C protein in the life cycle of CVBs.

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