FIG 9.

Model of the differential subversion of type I IFN and mitochondrial apoptotic pathway by LCMV. (A) In uninfected cells, a challenging RNA virus (VSV) induces IFN-I and mitochondrial apoptosis via RIG-I/MAVS involving TRAF2, -3, and -6, TBK1, Bax, and IRF3 (33). (B) In LCMV-infected cells, the IFN-I response, but not mitochondrial apoptosis, is blocked in response to superinfection. LCMV NP's 3′–5′ exoribonuclease activity may remove free viral RNA (scissors), preventing IRF3 phosphorylation, nuclear translocation, and, hence, IFN-I production. The ability of LCMV-infected cells to undergo rapid mitochondrial apoptosis via MAVS suggests that in the presence of LCMV, an unknown PRR (?) recognizes a yet undefined virus-derived pathogen-associated molecular pattern (PAMP) (?). Activation of MAVS may then result in mitochondrial apoptosis via TRAF2, -3, and -6, TBK1, Bax, and IRF3. Cyt c, cytochrome c.