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 |
|