Rabies virus nucleoprotein functions to evade activation of the RIG-I-mediated antiviral response

Tatsunori Masatani, Naoto Ito, Kenta Shimizu, Yuki Ito, Keisuke Nakagawa, Yoshiharu Sawaki, Hiroyuki Koyama, Makoto Sugiyama

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

The rabies virus Ni-CE strain causes nonlethal infection in adult mice after intracerebral inoculation, whereas the parental Nishigahara (Ni) strain kills mice. We previously reported that the chimeric CE(NiN) strain with the N gene from the Ni strain in the genetic background of the Ni-CE strain kills adult mice, indicating that the N gene is related to the different pathogenicities of Ni and Ni-CE strains. In the present study, to obtain an insight into the mechanism by which the N gene determines viral pathogenicity, we compared the effects of Ni, Ni-CE, and CE(NiN) infections on host gene expressions using a human neuroblastoma cell line. Microarray analysis of these infected cells revealed that the expression levels of particular genes in Ni- and CE(NiN)-infected cells, including beta interferon (IFN-p) and chemokine genes (i.e., CXCL10 and CCL5) were lower than those in Ni-CE-infected cells. We also demonstrated that Ni-CE infection activated the interferon regulatory factor 3 (IRF-3)-dependent IFN-p promoter and induced IRF-3 nuclear translocation more efficiently than did Ni or CE(NiN) infection. Furthermore, we showed that Ni-CE infection, but not Ni or CE(NiN) infection, strongly activates the IRF-3 pathway through activation of RIG-I, which is known as a cellular sensor of virus infection. These findings indicate that the N protein of rabies virus (Ni strain) has a function to evade the activation of RIG-I. To our knowledge, this is the first report that the Mononegavirales N protein functions to evade induction of host IFN and chemokines.

Original languageEnglish (US)
Pages (from-to)4002-4012
Number of pages11
JournalJournal of virology
Volume84
Issue number8
DOIs
StatePublished - Apr 1 2010

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Masatani, T., Ito, N., Shimizu, K., Ito, Y., Nakagawa, K., Sawaki, Y., Koyama, H., & Sugiyama, M. (2010). Rabies virus nucleoprotein functions to evade activation of the RIG-I-mediated antiviral response. Journal of virology, 84(8), 4002-4012. https://doi.org/10.1128/JVI.02220-09