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 agent||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||-|
|Dengue virus||Flaviviridae, Flavivirus||Inactivation of TRIM25||Subgenomic Flavivirus RNA (sfRNA)|
Table 2. Other viruses recognized by host RIG-I.
|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|