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. 2005 May;79(9):5241–5248. doi: 10.1128/JVI.79.9.5241-5248.2005

FIG. 2.

FIG. 2.

Activation of IRF-3 and IRF-7 by TLR-dependent pathways and intracellular virus. TLR3 and TLR4 activate the IRF kinases TBK1 and IKKi (not shown) through the TLR adapter TRIF, which has been shown to associate with TBK1 and IRF-3 (for details, see the text). Intracellular virus is recognized by RNA helicases RIG-I and MDA-5, which transmit signals downstream, probably to TBK1, through CARD interactions. IFN induction by TLR7 and TLR9 ligands depends on the TLR adapter MyD88 and involves a complex of MyD88, IRF-7, and TRAF6. TRAF6 is thought to activate an IRF-7 kinase (X) that awaits identification. The targets of some NNSV are indicated. Influenza virus NS1 protein prevents viral RNA from being recognized. The V proteins of paramyxoviruses, including SV5, mumps, and Hendra viruses, bind to MDA-5 and block downstream signaling. Ebola virus, RSV, and rabies virus interfere with activation of IRF-3 in virus-infected cells. For Ebola virus VP35, an inhibitory effect on TRIF-mediated TLR signaling has been observed. Rabies virus P was shown to inhibit TBK1-mediated phosphorylation of IRF-3. Measles virus and RSV can effectively block MyD88-dependent IFN induction by TLR7 and TLR9 ligands (for details, see the text).