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

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. © 2014 huang et al.