Paramyxovirus evasion of innate immunity: Diverse strategies for common targets

Figure 3 Type I interferon induction is inhibited by paramyxovirus interferon-antagonist proteins at multiple stages. Pathogen-associated molecular patterns (PAMPs) generated during virus infection, such as dsRNA, are recognised by PRRs including endosomal/surface expressed Toll-like receptor 3 (TLR3) and cytoplasmic retinoic acid-inducible gene-I (RIG-I)/melanoma differentiation associated protein 5 (MDA5). TLR3 signals through the adaptor molecule Toll/interleukin-1 receptor domain-containing adaptor inducing interferon (IFN)β (TRIF), which recruits tumor necrosis factor receptor-associated factor (TRAF)2 to activate the inhibitor of nuclear factor κB (NF-κB) kinase (IKK)α/β kinases to phosphorylate inhibitory inhibitor of NF-κB (IκB), triggering its degradation and activation/nuclear translocation of NF-κB. TLR3 signalling via TRAF3 results in phosphorylation/activation of IFN regulatory factor (IRF)-3, causing its homodimerisation, or heterodimerisation with IRF-7 in professional IFN producing/IFN-primed cells, and translocation into the nucleus where, with NF-κB and activating transcription factor 2 (ATF2)/c-jun (not shown), it activates early type I IFN transcription. RIG-I and MDA5 also induce phosphorylation of IRF-3 following recognition of cytoplasmic PAMPs in infected cells via interaction with the mitochondrial membrane protein IFNβ promoter stimulator 1 (IPS-1), which recruits and activates TANK and the TANK-binding kinases (TBKs). TBK-1 and IKKε via the E3 ubiquitin ligase TRAF3. Many paramyxoviruses target this pathway; steps commonly targeted are indicated (black bars) with specific examples of the paramyxovirus proteins responsible (see text for details). DC: Dendritic cell; PIV5: Parainfluenza virus 5; MeV: Measles virus; MuV: Mumps virus; SeV: Sendai virus; hPIV: Human PIV; HeV: Hendra virus; NiV: Nipah virus; SalV: Salem virus; TioV: Tioman virus; NDV: Newcastle disease virus; MPRV: Mapuera virus; MenV: Menangle virus; PoRV: Porcine rubulavirus; LGP2: Laboratory of genetics and physiology 2.