論文

基本情報

氏名 児島 一州
氏名(カナ) コジマ イッシュウ
氏名(英語) Kojima Isshu
所属 獣医学部 獣医学科
職名 助教
researchmap研究者コード R000055330
researchmap機関 岡山理科大学

題名

The Amino Acid at Position 95 in the Matrix Protein of Rabies Virus Is Involved in Antiviral Stress Granule Formation in Infected Cells.

単著・共著の別

共著

著者

Isshu Kojima/Koji Onomoto/Wenjie Zuo/Makoto Ozawa/Kosuke Okuya/Kiyotada Naitou/Fumiki Izumi/Misuzu Okajima/Takuro Fujiwara/Naoto Ito/Mitsutoshi Yoneyama/Kentaro Yamada/Akira Nishizono/Makoto Sugiyama/Takashi Fujita/Tatsunori Masatani

概要

Stress granules (SGs) are dynamic structures that store cytosolic messenger ribonucleoproteins. SGs have recently been shown to serve as a platform for activating antiviral innate immunity; however, several pathogenic viruses suppress SG formation to evade innate immunity. In this study, we investigated the relationship between rabies virus (RABV) virulence and SG formation, using viral strains with different levels of virulence. We found that the virulent Nishigahara strain did not induce SG formation, but its avirulent offshoot, the Ni-CE strain, strongly induced SG formation. Furthermore, we demonstrated that the amino acid at position 95 in the RABV matrix protein (M95), a pathogenic determinant for the Nishigahara strain, plays a key role in inhibiting SG formation, followed by protein kinase R (PKR)-dependent phosphorylation of the α subunit of eukaryotic initiation factor 2α (eIF2α). M95 was also implicated in the accumulation of RIG-I, a viral RNA sensor protein, in SGs and in the subsequent acceleration of interferon induction. Taken together, our findings strongly suggest that M95-related inhibition of SG formation contributes to the pathogenesis of RABV by allowing the virus to evade the innate immune responses of the host. IMPORTANCE Rabies virus (RABV) is a neglected zoonotic pathogen that causes lethal infections in almost all mammalian hosts, including humans. Recently, RABV has been reported to induce intracellular formation of stress granules (SGs), also known as platforms that activate innate immune responses. However, the relationship between SG formation capacity and pathogenicity of RABV has remained unclear. In this study, by comparing two RABV strains with completely different levels of virulence, we found that the amino acid mutation from valine to alanine at position 95 of matrix protein (M95), which is known to be one of the amino acid mutations that determine the difference in virulence between the strains, plays a major role in SG formation. Importantly, M95 was involved in the accumulation of RIG-I in SGs and in promoting interferon induction. These findings are the first report of the effect of a single amino acid substitution associated with SGs on viral virulence.

発表雑誌等の名称

Journal of virology

出版者

96

18

開始ページ

e0081022

終了ページ

発行又は発表の年月

2022/09

査読の有無

有り

招待の有無

記述言語

英語

掲載種別

研究論文(学術雑誌)

ISSN

ID:DOI

10.1128/jvi.00810-22

ID:NAID(CiNiiのID)

ID:PMID

JGlobalID

arXiv ID

ORCIDのPut Code

DBLP ID