Virus-Infection or 5′ppp-RNA Activates Antiviral Signal through Redistribution of IPS-1 Mediated by MFN1

PLoS Pathogens

Kazuhide Onoguchi¹  Azumi Takemura¹  Michihiko Jogi¹  Takashi Fujita¹  Ilkka Julkunen¹  Mitsutoshi Yoneyama¹  Hideo Namiki²  Shiho Morimoto²  Koji Onomoto²  Shiori Takamatsu³ 

[1] Department of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan;Graduate School of Biostudies, Kyoto University, Yoshida-Konoe Sakyo, Kyoto, Japan;Graduate School of Science and Engineering, Waseda University, Tokyo, Japan

关键词: Mitochondria;    Antibodies;    Small interfering RNAs;    Cell staining;    Cloning;    HeLa cells;    Viral transmission;    infection;    Antiviral immune response;   

DOI  :  10.1371/journal.ppat.1001012

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

In virus-infected cells, RIG-I-like receptor (RLR) recognizes cytoplasmic viral RNA and triggers innate immune responses including production of type I and III interferon (IFN) and the subsequent expression of IFN-inducible genes. Interferon-β promoter stimulator 1 (IPS-1, also known as MAVS, VISA and Cardif) is a downstream molecule of RLR and is expressed on the outer membrane of mitochondria. While it is known that the location of IPS-1 is essential to its function, its underlying mechanism is unknown. Our aim in this study was to delineate the function of mitochondria so as to identify more precisely its role in innate immunity. In doing so we discovered that viral infection as well as transfection with 5′ppp-RNA resulted in the redistribution of IPS-1 to form speckle-like aggregates in cells. We further found that Mitofusin 1 (MFN1), a key regulator of mitochondrial fusion and a protein associated with IPS-1 on the outer membrane of mitochondria, positively regulates RLR-mediated innate antiviral responses. Conversely, specific knockdown of MFN1 abrogates both the virus-induced redistribution of IPS-1 and IFN production. Our study suggests that mitochondria participate in the segregation of IPS-1 through their fusion processes.

【 授权许可】

CC BY