RIG-I inhibition

Upon viral infection, the cellular cytosolic receptor RIG-I(AF038963:9606) recognizes viral RNA in a 5'-triphosphate-dependent manner and initiates an antiviral signaling cascade characterized by expression of antiviral cytokines and interferons. The RIG-I(AF038963:9606) protein belongs to the helicase family and the interaction with its downstream adaptor molecule MAVS is triggered by RIG-I(AF038963:9606) ubiquitination mediated by TRIM25(D21205:9606).

Z NS1 NS2 RIGI RIGI STING TRIM25 MAVS TRADD TRADD TRAF3 TRAF6 TRAF2 FADD RIP1 TBK1 IKKe IRF3 IRF3 IRF7 IRF7 IKb IKb DDX3 IKKgamma IKKalpha IKKbeta NFKB NFKB NFKB

Many viruses encode proteins that directly interfere with RIG-I(AF038963:9606) to inhibit interferon production. A specific viral protease encoded by Poliovirus termed the 3Cpro(P03300) cleaves RIG-I(AF038963:9606) and abrogates its activity. This cleavage is likely to occur in all picornaviruses . The Z(AF038963:9606) protein of new world arenaviruses directly binds RIG-I(AF038963:9606) and interferes with type I interferon production. The interaction blocks RIG-I(AF038963:9606) interaction with MAVS, the downstream partner in the cascade. Other viral proteins targeting RIG-I(AF038963:9606) include NS2(P24569) form HRSV or G(Q6WB94) protein from human metapneumovirus.


Table 1. Viruses recognized by host RIG-I and mechanisms of evasion employed to counteract the immune response initiated by RIG-I.

Virus Family Method of evasion Viral protein References
Respiratory syncytial virus Paramyxoviridae, Pneumovirus Direct interaction with RIG-I NS2(O42038)
Rabies virus Rhabdoviridae, Lyssavirus Protect RNA from RIG-I recognition Nucleoprotein(P06025)
Influenza A virus Orthomyxoviridae, Influenzavirus A Prevent RIG-I ubiquitination NS1(P03496)
New world arenaviruses Arenaviridae, Arenavirus Direct interaction with RIG-I Z(Q6UY71)
Hantaan virus Bunyaviridae, Hantavirus Processing of viral genome 5' termini -
Crimean-Congo hemorrhagic fever virus Bunyaviridae, Nairovirus Processing of viral genome 5' termini -
Borna disease virus Bornaviridae, Bornavirus Processing of viral genome 5' termini -

Table 2. Other viruses recognized by host RIG-I.
Virus Family References
Rift valley virus Bunyaviridae, Phlebovirus
Vesicular stomatitis virus Rhabdoviridae, Vesiculovirus
Sendai virus Paramyxoviridae, Respirovirus
Measles virus Paramyxoviridae, Morbillivirus
New Castle disease virus Paramyxoviridae, Respirovirus
Ebola virus Filoviridae, Ebolavirus
Nipah virus Paramyxoviridae, Henipavirus
Old world arenaviruses Arenaviridae, Arenavirus
Influenza B virus Orthomyxoviridae, Influenza B virus