RIG-I inhibition

Upon viral infection, the cellular cytosolic receptor RIG-I 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 protein belongs to the helicase family and the interaction with its downstream adaptor molecule MAVS is triggered by RIG-I ubiquitination mediated by TRIM25.

Many viruses encode proteins that directly interfere with RIG-I to inhibit interferon production. A specific viral protease encoded by Poliovirus termed the 3Cpro cleaves RIG-I and abrogates its activity. This cleavage is likely to occur in all picornaviruses . The Z protein of new world arenaviruses directly binds RIG-I and interferes with type I interferon production. The interaction blocks RIG-I interaction with MAVS, the downstream partner in the cascade. Other viral proteins targeting RIG-I include NS2 form HRSV or G 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
Rabies virus	Rhabdoviridae, Lyssavirus	Protect RNA from RIG-I recognition	Nucleoprotein
Influenza A virus	Orthomyxoviridae, Influenzavirus A	Prevent RIG-I ubiquitination	NS1
New world arenaviruses	Arenaviridae, Arenavirus	Direct interaction with RIG-I	Z
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