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

65 Citations (Scopus)

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 2010
Externally publishedYes

Fingerprint

Rabies virus
nucleoproteins
Nucleoproteins
Antiviral Agents
Interferon Regulatory Factor-3
Infection
infection
Chemokines
Genes
chemokines
Mononegavirales
Virulence
genes
Tissue Array Analysis
mice
pathogenicity
interferon-beta
Viral Genes
Interferon-beta
Virus Diseases

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Masatani, T., Ito, N., Shimizu, K., Ito, Y., Nakagawa, K., Sawaki, Y., ... 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

Rabies virus nucleoprotein functions to evade activation of the RIG-I-mediated antiviral response. / Masatani, Tatsunori; Ito, Naoto; Shimizu, Kenta; Ito, Yuki; Nakagawa, Keisuke; Sawaki, Yoshiharu; Koyama, Hiroyuki; Sugiyama, Makoto.

In: Journal of Virology, Vol. 84, No. 8, 04.2010, p. 4002-4012.

Research output: Contribution to journalArticle

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, vol. 84, no. 8, pp. 4002-4012. https://doi.org/10.1128/JVI.02220-09
Masatani, Tatsunori ; Ito, Naoto ; Shimizu, Kenta ; Ito, Yuki ; Nakagawa, Keisuke ; Sawaki, Yoshiharu ; Koyama, Hiroyuki ; Sugiyama, Makoto. / Rabies virus nucleoprotein functions to evade activation of the RIG-I-mediated antiviral response. In: Journal of Virology. 2010 ; Vol. 84, No. 8. pp. 4002-4012.
@article{01d97d73591745e689119016de8e138e,
title = "Rabies virus nucleoprotein functions to evade activation of the RIG-I-mediated antiviral response",
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.",
author = "Tatsunori Masatani and Naoto Ito and Kenta Shimizu and Yuki Ito and Keisuke Nakagawa and Yoshiharu Sawaki and Hiroyuki Koyama and Makoto Sugiyama",
year = "2010",
month = "4",
doi = "10.1128/JVI.02220-09",
language = "English (US)",
volume = "84",
pages = "4002--4012",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "8",

}

TY - JOUR

T1 - Rabies virus nucleoprotein functions to evade activation of the RIG-I-mediated antiviral response

AU - Masatani, Tatsunori

AU - Ito, Naoto

AU - Shimizu, Kenta

AU - Ito, Yuki

AU - Nakagawa, Keisuke

AU - Sawaki, Yoshiharu

AU - Koyama, Hiroyuki

AU - Sugiyama, Makoto

PY - 2010/4

Y1 - 2010/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77950501526&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950501526&partnerID=8YFLogxK

U2 - 10.1128/JVI.02220-09

DO - 10.1128/JVI.02220-09

M3 - Article

VL - 84

SP - 4002

EP - 4012

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 8

ER -