Role of interferon antagonist activity of rabies virus phosphoprotein in viral pathogenicity

Naoto Ito, Gregory William Moseley, Danielle Blondel, Kenta Shimizu, Caitlin Lorraine Rowe, Yuki Ito, Tatsunori Masatani, Keisuke Nakagawa, David Andrew Jans, Makoto Sugiyama

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The fixed rabies virus (RV) strain, Nishigahara, kills adult mice after intracerebral inoculation, whereas the chicken embryo fibroblast cell-adapted strain Ni-CE causes non-lethal infection in adult mice. We previously reported that the chimeric CE(NiP) strain, which has the phosphoprotein (P protein) gene from Nishigahara strain in the genetic background of Ni-CE strain, causes lethal infection in adult mice, indicating that the P gene is responsible for the different pathogenicities of Nishigahara and Ni-CE strains. Previous studies demonstrated that RV P protein binds to the interferon (IFN)-activated transcription factor STAT1, and blocks IFN signaling by preventing its translocation to the nucleus. In this study, we examine the molecular mechanism by which RV P protein determines viral pathogenicity by comparing IFN-antagonist activities of Nishigahara and Ni-CE P proteins. The results, obtained from both RV-infected cells and cells transfected to express P protein only, show that Ni-CE P protein is significantly impaired for its capacity to block IFN-activated STAT1 nuclear translocation and, consequently, inhibits IFN signaling less efficiently than Nishigahara P protein. Further, it was demonstrated that a defect in the nuclear export of Ni-CE P protein correlates with a defect in its ability to cause the mislocalization of STAT1. These data provide the first evidence that the capacity of the RV P protein to inhibit STAT1 nuclear translocation and IFN signaling correlates with the viral pathogenicity.
Original languageEnglish
Pages (from-to)6699 - 6710
Number of pages12
JournalJournal of Virology
Volume84
Issue number13
DOIs
Publication statusPublished - 2010

Cite this

Ito, Naoto ; Moseley, Gregory William ; Blondel, Danielle ; Shimizu, Kenta ; Rowe, Caitlin Lorraine ; Ito, Yuki ; Masatani, Tatsunori ; Nakagawa, Keisuke ; Jans, David Andrew ; Sugiyama, Makoto. / Role of interferon antagonist activity of rabies virus phosphoprotein in viral pathogenicity. In: Journal of Virology. 2010 ; Vol. 84, No. 13. pp. 6699 - 6710.
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abstract = "The fixed rabies virus (RV) strain, Nishigahara, kills adult mice after intracerebral inoculation, whereas the chicken embryo fibroblast cell-adapted strain Ni-CE causes non-lethal infection in adult mice. We previously reported that the chimeric CE(NiP) strain, which has the phosphoprotein (P protein) gene from Nishigahara strain in the genetic background of Ni-CE strain, causes lethal infection in adult mice, indicating that the P gene is responsible for the different pathogenicities of Nishigahara and Ni-CE strains. Previous studies demonstrated that RV P protein binds to the interferon (IFN)-activated transcription factor STAT1, and blocks IFN signaling by preventing its translocation to the nucleus. In this study, we examine the molecular mechanism by which RV P protein determines viral pathogenicity by comparing IFN-antagonist activities of Nishigahara and Ni-CE P proteins. The results, obtained from both RV-infected cells and cells transfected to express P protein only, show that Ni-CE P protein is significantly impaired for its capacity to block IFN-activated STAT1 nuclear translocation and, consequently, inhibits IFN signaling less efficiently than Nishigahara P protein. Further, it was demonstrated that a defect in the nuclear export of Ni-CE P protein correlates with a defect in its ability to cause the mislocalization of STAT1. These data provide the first evidence that the capacity of the RV P protein to inhibit STAT1 nuclear translocation and IFN signaling correlates with the viral pathogenicity.",
author = "Naoto Ito and Moseley, {Gregory William} and Danielle Blondel and Kenta Shimizu and Rowe, {Caitlin Lorraine} and Yuki Ito and Tatsunori Masatani and Keisuke Nakagawa and Jans, {David Andrew} and Makoto Sugiyama",
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Ito, N, Moseley, GW, Blondel, D, Shimizu, K, Rowe, CL, Ito, Y, Masatani, T, Nakagawa, K, Jans, DA & Sugiyama, M 2010, 'Role of interferon antagonist activity of rabies virus phosphoprotein in viral pathogenicity', Journal of Virology, vol. 84, no. 13, pp. 6699 - 6710. https://doi.org/10.1126/JVI.00011-10

Role of interferon antagonist activity of rabies virus phosphoprotein in viral pathogenicity. / Ito, Naoto; Moseley, Gregory William; Blondel, Danielle; Shimizu, Kenta; Rowe, Caitlin Lorraine; Ito, Yuki; Masatani, Tatsunori; Nakagawa, Keisuke; Jans, David Andrew; Sugiyama, Makoto.

In: Journal of Virology, Vol. 84, No. 13, 2010, p. 6699 - 6710.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Ito, Naoto

AU - Moseley, Gregory William

AU - Blondel, Danielle

AU - Shimizu, Kenta

AU - Rowe, Caitlin Lorraine

AU - Ito, Yuki

AU - Masatani, Tatsunori

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AU - Sugiyama, Makoto

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