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.
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 |