Inhibition of host RIG-I by virus

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.

Z NS1 NS2 RIGI RIGI STING TRIM25 MAVS TRADD TRADD TRAF3 TRAF2 TRAF6 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 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

Matching UniProtKB/Swiss-Prot entries

113 entries grouped by protein (browse by keywords)

Only complete proteome entries are shown (view all 189 entries)

Non-structural protein 1 (NS1) (NS1A)

Select_all Deselect_all  
NS1_I96A0Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd) reference strain
NS1_I34A1Influenza A virus (strain A/Puerto Rico/8/1934 H1N1) reference strain
NS1_I75A0Influenza A virus (strain A/Beijing/39/1975 H3N2)
NS1_I77AAInfluenza A virus (strain A/Brazil/11/1978 H1N1)
NS1_I18A0Influenza A virus (strain A/Brevig Mission/1/1918 H1N1) (Influenza A virus ...
NS1_I83A5Influenza A virus (strain A/Chicken/Pennsylvania/1/1983 H5N2)
NS1_I59A0Influenza A virus (strain A/Chicken/Scotland/1959 H5N1)
NS1_I83A1Influenza A virus (strain A/Chile/1/1983 H1N1)
NS1_I96A3Influenza A virus (strain A/China:Nanchang/11/1996 H1N1)
NS1_I56A1Influenza A virus (strain A/Duck/Czechoslovakia/1956 H4N6)
NS1_I56A2Influenza A virus (strain A/Duck/England/1/1956 H11N6)
NS1_I49A1Influenza A virus (strain A/Duck/Germany/1949 H10N7)
NS1_I80A6Influenza A virus (strain A/Duck/Hokkaido/8/1980 H3N8)
NS1_I00A0Influenza A virus (strain A/Duck/Hong Kong/2986.1/2000 H5N1 genotype C)
NS1_I79A7Influenza A virus (strain A/Grey teal/Australia/2/1979 H4N4)
NS1_I77AFInfluenza A virus (strain A/Gull/Maryland/704/1977 H13N6)
NS1_I80ADInfluenza A virus (strain A/Gull/Minnesota/945/1980 H13N6)
NS1_I36A0Influenza A virus (strain A/Henry/1936 H1N1)
NS1_I40A0Influenza A virus (strain A/Hickox/1940 H1N1)
NS1_I68A4Influenza A virus (strain A/Hong Kong/1/1968 H3N2)
NS1_I97A1Influenza A virus (strain A/Hong Kong/156/1997 H5N1 genotype Gs/Gd)
NS1_I83A8Influenza A virus (strain A/Hong Kong/5/1983 H3N2)
NS1_I80AAInfluenza A virus (strain A/India/6263/1980 H1N1)
NS1_I54A2Influenza A virus (strain A/Malaysia:Malaya/302/1954 H1N1)
NS1_I71A1Influenza A virus (strain A/Memphis/1/1971 H3N2)
NS1_I72A4Influenza A virus (strain A/Memphis/101/1972 H3N2)
NS1_I72A3Influenza A virus (strain A/Memphis/102/1972 H3N2)
NS1_I76A6Influenza A virus (strain A/Memphis/110/1976 H3N2)
NS1_I78A8Influenza A virus (strain A/Memphis/18/1978 H3N2)
NS1_I78A7Influenza A virus (strain A/Memphis/2/1978 H3N2)
NS1_I80A4Influenza A virus (strain A/Memphis/4/1980 H3N2)
NS1_I73A5Influenza A virus (strain A/Port Chalmers/1/1973 H3N2)
NS1_I06A0Influenza A virus (strain A/Russia:St.Petersburg/8/2006 H1N1)
NS1_I80A2Influenza A virus (strain A/Seal/Massachusetts/1/1980 H7N7)
NS1_I57A5Influenza A virus (strain A/Singapore/1/1957 H2N2)
NS1_I77A4Influenza A virus (strain A/Swine/Colorado/1/1977 H3N2)
NS1_I61A1Influenza A virus (strain A/Swine/Wisconsin/1/1961 H1N1)
NS1_I83A4Influenza A virus (strain A/Turkey/Ireland/1378/1983 H5N8)
NS1_I80A8Influenza A virus (strain A/Turkey/Minnesota/833/1980 H4N2)
NS1_I68A3Influenza A virus (strain A/Turkey/Ontario/6118/1968 H8N4)
NS1_I66A1Influenza A virus (strain A/Turkey/Wisconsin/1/1966 H9N2)
NS1_I72A2Influenza A virus (strain A/Udorn/307/1972 H3N2)
NS1_I51A0Influenza A virus (strain A/USA:Albany/12/1951 H1N1)
NS1_I45A0Influenza A virus (strain A/USA:Huston/AA/1945 H1N1)
NS1_I43A0Influenza A virus (strain A/USA:Iowa/1943 H1N1)
NS1_I96A2Influenza A virus (strain A/USA:Memphis/10/1996 H1N1)
NS1_I35A3Influenza A virus (strain A/USA:Phila/1935 H1N1)
NS1_I33A0Influenza A virus (strain A/Wilson-Smith/1933 H1N1) (Influenza A virus (strain ...

Non-structural protein 2 (NS2) (Non-structural protein 1B)

Select_all Deselect_all  
NS2_HRSVBHuman respiratory syncytial virus B (strain B1) reference strain
NS2_BRSVABovine respiratory syncytial virus (strain A51908) (BRS)
NS2_HRSVAHuman respiratory syncytial virus A (strain A2)

Genome polyprotein

Select_all Deselect_all  
POLG_EMCVREncephalomyocarditis virus (strain Rueckert) (EMCV) reference strain
POLG_HRV8AHuman rhinovirus A serotype 89 (strain 41467-Gallo) (HRV-89) reference strain
POLG_POL1MPoliovirus type 1 (strain Mahoney) reference strain
POLG_BOVEVBovine enterovirus (strain VG-5-27) (BEV)
POLG_CX16GCoxsackievirus A16 (strain G-10)
POLG_CX16TCoxsackievirus A16 (strain Tainan/5079/98)
POLG_CXA21Coxsackievirus A21 (strain Coe)
POLG_CXA24Coxsackievirus A24 (strain EH24/70)
POLG_CXA9Coxsackievirus A9 (strain Griggs)
POLG_CXB1JCoxsackievirus B1 (strain Japan)
POLG_CXB2OCoxsackievirus B2 (strain Ohio-1)
POLG_CXB3NCoxsackievirus B3 (strain Nancy)
POLG_CXB3WCoxsackievirus B3 (strain Woodruff)
POLG_CXB4ECoxsackievirus B4 (strain E2)
POLG_CXB4JCoxsackievirus B4 (strain JVB / Benschoten / New York/51)
POLG_CXB5PCoxsackievirus B5 (strain Peterborough / 1954/UK/85)
POLG_CXB6SCoxsackievirus B6 (strain Schmitt)
POLG_EC01FEchovirus 1 (strain Human/Egypt/Farouk/1951) (E-1)
POLG_EC11GEchovirus 11 (strain Gregory)
POLG_EC12TEchovirus 12 (strain Travis)
POLG_EC30BEchovirus 30 (strain Bastianni)
POLG_EC05NEchovirus 5 (strain Noyce)
POLG_EC06CEchovirus 6 (strain Charles)
POLG_EC09BEchovirus 9 (strain Barty)
POLG_EC09HEchovirus 9 (strain Hill)
POLG_EMCVEncephalomyocarditis virus
POLG_EMCVBEncephalomyocarditis virus (strain emc-b nondiabetogenic)
POLG_EMCVDEncephalomyocarditis virus (strain emc-d diabetogenic)
POLG_HE701Human enterovirus 70 (strain J670/71) (EV 70)
POLG_HE71MHuman enterovirus 71 (strain 7423/MS/87) (Ev 71)
POLG_HE71BHuman enterovirus 71 (strain BrCr) (Ev 71)
POLG_HRV14Human rhinovirus 14 (HRV-14)
POLG_HRV16Human rhinovirus 16 (HRV-16)
POLG_HRV1AHuman rhinovirus 1A (HRV-1A)
POLG_HRV1BHuman rhinovirus 1B (HRV-1B)
POLG_HRV2Human rhinovirus 2 (HRV-2)
POLG_HRV3Human rhinovirus 3 (HRV-3)
POLG_ENMGOMengo encephalomyocarditis virus
POLG_POL1SPoliovirus type 1 (strain Sabin)
POLG_POL2LPoliovirus type 2 (strain Lansing)
POLG_POL2WPoliovirus type 2 (strain W-2)
POLG_POL32Poliovirus type 3 (strain 23127)
POLG_POL3LPoliovirus type 3 (strains P3/Leon/37 and P3/Leon 12A[1]B)
POLG_PEV9UPorcine enterovirus 9 (strain UKG/410/73)
POLG_SVDVHSwine vesicular disease virus (strain H/3 '76) (SVDV)
POLG_SVDVUSwine vesicular disease virus (strain UKG/27/72) (SVDV)
POLG_TMEVGTheiler's murine encephalomyelitis virus (strain GDVII) (TMEV)

Major surface glycoprotein G (Attachment glycoprotein G) (Membrane-bound glycoprotein) (mG)


VGLG_HMPVCHuman metapneumovirus (strain CAN97-83) (HMPV) reference strain

RING finger protein Z (Protein Z) (Zinc-binding protein)

Select_all Deselect_all  
Z_TACVFTacaribe virus (strain Franze-Fernandez) (TCRV) reference strain
Z_ALLVPAllpahuayo virus (isolate Rat/Peru/CLHP-2472/1997) (ALLV)
Z_BCNVUBear canyon virus (isolate Mouse/United States/AV A0070039/2000) (BCNV)
Z_CHAVBChapare virus (isolate Human/Bolivia/810419/2003)
Z_CPXVBCupixi virus (isolate Rat/Brasil/BeAn 119303/1970) (CPXV)
Z_GTOVVGuanarito virus (isolate Human/Venezuela/NH-95551/1990) (GTOV)
Z_LATVBLatino virus (isolate Rat/Bolivia/MARU 1924/1965) (LATV)
Z_MACHUMachupo virus (MACV)
Z_OLVVAOliveros virus (isolate Mouse/Argentina/RIID 3229/1990) (OLVV)
Z_PARVPParana virus (isolate Rat/Paraguay/12056/1965) (PARV)
Z_PIRVVPirital virus (isolate Rat/Venezuela/VAV-488/1995) (PIRV)
Z_SABVBSabia virus (isolate Human/Brasil/SPH114202/1990) (SABV)
Z_TAMVUTamiami virus (isolate Rat/United States/W 10777/1964) (TAMV)
Z_WWAVUWhitewater arroyo virus (isolate Rat/United States/AV 9310135/1995) (WWAV)