MAVS-MKK7-JNK2 Defines a Novel Apoptotic Signaling Pathway during Viral Infection

PLoS Pathogens

Senlin Li¹  Bo Wei¹  Heng Liu¹  Yuefeng Huang¹  Huansha Yu¹  Yijun Tang¹  Chen Wang¹ 

[1] State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

关键词: Apoptosis;    Mitochondria;    Small interfering RNAs;    Phosphorylation;    Viral transmission;    infection;    Vesicular stomatitis virus;    Immunoprecipitation;    Cell signaling;   

DOI  :  10.1371/journal.ppat.1004020

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Viral infection induces innate immunity and apoptosis. Apoptosis is an effective means to sacrifice virus-infected host cells and therefore restrict the spread of pathogens. However, the underlying mechanisms of this process are still poorly understood. Here, we show that the mitochondrial antiviral signaling protein (MAVS/VISA/Cardif/IPS-1) is critical for SeV (Sendai virus)-induced apoptosis. MAVS specifically activates c-Jun N-terminal kinase 2 (JNK2) but not other MAP kinases. Jnk2−/− cells, but not Jnk1−/− cells, are unable to initiate virus-induced apoptosis and SeV further fails to trigger apoptosis in MAPK kinase 7 (MKK7) knockout (Mkk7−/−) cells. Mechanistically, MAVS recruits MKK7 onto mitochondria via its 3D domain, which subsequently phosphorylates JNK2 and thus activates the apoptosis pathway. Consistently, Jnk2−/− mice, but not Jnk1−/− mice, display marked inflammatory injury in lung and liver after viral challenge. Collectively, we have identified a novel signaling pathway, involving MAVS-MKK7-JNK2, which mediates virus-induced apoptosis and highlights the indispensable role of mitochondrial outer membrane in host defenses.

【 授权许可】

CC BY