Inhibition of host RIG-I by virus (kw:KW-1088)

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 image. 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

Matching UniProtKB/Swiss-Prot entries

(all links/actions below point to uniprot.org website)

200 entries grouped by protein

1 entry

F protein (Alternate reading frame protein/F-protein) (ARFP/F) (Frameshifted protein) (p16) (p17)

F_HCV77
Hepatitis C virus genotype 1a (isolate H77) (HCV) reference strain

1 entry

Inner tegument protein (EC 3.5.1.-) (EC 3.5.1.44) (Viral deamidase UL37)

ITP_HHV11
Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) reference strain

130 entries

Non-structural protein 1 (NS1) (NS1A)

Select_allDeselect_all
NS1_BRSVA
Bovine respiratory syncytial virus (strain A51908) (BRS) reference strain

Non-structural protein 1 (Non-structural protein 1C)

NS1_HRSVB
Human respiratory syncytial virus B (strain B1) reference strain

Non-structural protein 1 (Non-structural protein 1C)

NS1_I34A1
Influenza A virus (strain A/Puerto Rico/8/1934 H1N1) reference strain
NS1_I96A0
Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd) reference strain
NS1_INCAA
Influenza C virus (strain C/Ann Arbor/1/1950) reference strain
NS1_HRSS2
Human respiratory syncytial virus A (strain S-2) (HRSV-S2)

Non-structural protein 1 (NS1) (Non-structural protein 1C)

NS1_HRSV
Human respiratory syncytial virus

Non-structural protein 1 (Non-structural protein 1C)

NS1_HRSV1
Human respiratory syncytial virus B (strain 18537)

Non-structural protein 1 (Non-structural protein 1C)

NS1_HRSVA
Human respiratory syncytial virus A (strain A2)

Non-structural protein 1 (NS1) (Non-structural protein 1C)

NS1_I000W
Influenza A virus (strain A/Wa-182)
NS1_I000X
Influenza A virus (strain A/X-31 H3N2)
NS1_I00A0
Influenza A virus (strain A/Duck/Hong Kong/2986.1/2000 H5N1 genotype C)
NS1_I00A1
Influenza A virus (strain A/New Zealand:South Canterbury/35/2000 H1N1)
NS1_I01A0
Influenza A virus (strain A/Silky Chicken/Hong Kong/SF189/2001 H5N1 genotype A)
NS1_I01A1
Influenza A virus (strain A/Chicken/Hong Kong/YU562/2001 H5N1 genotype B)
NS1_I01A2
Influenza A virus (strain A/Chicken/Hong Kong/FY150/2001 H5N1 genotype D)
NS1_I01A3
Influenza A virus (strain A/Chicken/Hong Kong/715.5/2001 H5N1 genotype E)
NS1_I02A0
Influenza A virus (strain A/Chicken/Brescia/1902 H7N7)
NS1_I02A1
Influenza A virus (strain A/Guinea fowl/Hong Kong/38/2002 H5N1 genotype X0)
NS1_I02A2
Influenza A virus (strain A/Chicken/Hong Kong/31.2/2002 H5N1 genotype X1)
NS1_I02A3
Influenza A virus (strain A/Chicken/Hong Kong/37.4/2002 H5N1 genotype X2)
NS1_I02A4
Influenza A virus (strain A/Silky Chicken/Hong Kong/YU100/2002 H5N1 genotype X3)
NS1_I02A5
Influenza A virus (strain A/Chicken/Hong Kong/96.1/2002 H5N1 genotype Y)
NS1_I02A6
Influenza A virus (strain A/Chicken/Hong Kong/YU22/2002 H5N1 genotype Z)
NS1_I03A0
Influenza A virus (strain A/Hong Kong/212/2003 H5N1 genotype Z+)
NS1_I03A1
Influenza A virus (strain A/Chicken/Shantou/4231/2003 H5N1 genotype V)
NS1_I06A0
Influenza A virus (strain A/Russia:St.Petersburg/8/2006 H1N1)
NS1_I07A0
Influenza A virus (strain A/USA:Texas/UR06-0195/2007 H1N1)
NS1_I18A0
Influenza A virus (strain A/Brevig Mission/1/1918 H1N1) (Influenza A virus (strain A/South Carolina/1/1918 H1N1))
NS1_I30A0
Influenza A virus (strain A/Swine/Iowa/15/1930 H1N1)
NS1_I33A0
Influenza A virus (strain A/Wilson-Smith/1933 H1N1) (Influenza A virus (strain A/WS/1933 H1N1))
NS1_I34A0
Influenza A virus (strain A/Fowl plague virus/Rostock/8/1934 H7N1)
NS1_I35A3
Influenza A virus (strain A/USA:Phila/1935 H1N1)
NS1_I36A0
Influenza A virus (strain A/Henry/1936 H1N1)
NS1_I40A0
Influenza A virus (strain A/Hickox/1940 H1N1)
NS1_I43A0
Influenza A virus (strain A/USA:Iowa/1943 H1N1)
NS1_I45A0
Influenza A virus (strain A/USA:Huston/AA/1945 H1N1)
NS1_I47A0
Influenza A virus (strain A/Fort Monmouth/1/1947 H1N1)
NS1_I49A0
Influenza A virus (strain A/Chicken/Germany/n/1949 H10N7)
NS1_I49A1
Influenza A virus (strain A/Duck/Germany/1949 H10N7)
NS1_I50A0
Influenza A virus (strain A/Fort Warren/1/1950 H1N1)
NS1_I51A0
Influenza A virus (strain A/USA:Albany/12/1951 H1N1)
NS1_I54A0
Influenza A virus (strain A/Leningrad/1/1954 H1N1)
NS1_I54A2
Influenza A virus (strain A/Malaysia:Malaya/302/1954 H1N1)
NS1_I56A1
Influenza A virus (strain A/Duck/Czechoslovakia/1956 H4N6)
NS1_I56A2
Influenza A virus (strain A/Duck/England/1/1956 H11N6)
NS1_I56A3
Influenza A virus (strain A/Equine/Prague/1/1956 H7N7)
NS1_I57A0
Influenza A virus (strain A/Japan/305/1957 H2N2)
NS1_I57A1
Influenza A virus (strain A/Leningrad/134/1957 H2N2)
NS1_I57A2
Influenza A virus (strain A/Leningrad/134/17/1957 H2N2)
NS1_I57A3
Influenza A virus (strain A/Leningrad/134/47/1957 H2N2)
NS1_I57A5
Influenza A virus (strain A/Singapore/1/1957 H2N2)
NS1_I59A0
Influenza A virus (strain A/Chicken/Scotland/1959 H5N1)
NS1_I60A0
Influenza A virus (strain A/Ann Arbor/6/1960 H2N2)
NS1_I61A1
Influenza A virus (strain A/Swine/Wisconsin/1/1961 H1N1)
NS1_I63A1
Influenza A virus (strain A/Turkey/Canada/1963 H6N8)
NS1_I66A0
Influenza A virus (strain A/Turkey/Ontario/7732/1966 H5N9)
NS1_I66A1
Influenza A virus (strain A/Turkey/Wisconsin/1/1966 H9N2)
NS1_I67A0
Influenza A virus (strain A/Tokyo/3/1967 H2N2)
NS1_I68A0
Influenza A virus (strain A/Aichi/2/1968 H3N2)
NS1_I68A3
Influenza A virus (strain A/Turkey/Ontario/6118/1968 H8N4)
NS1_I68A4
Influenza A virus (strain A/Hong Kong/1/1968 H3N2)
NS1_I68A5
Influenza A virus (strain A/Korea/426/1968 H2N2)
NS1_I69A0
Influenza A virus (strain A/England/878/1969 H3N2)
NS1_I70A0
Influenza A virus (strain A/Qu/7/1970 H3N2)
NS1_I71A1
Influenza A virus (strain A/Memphis/1/1971 H3N2)
NS1_I71A2
Influenza A virus (strain A/Turkey/Oregon/1971 H7N3)
NS1_I72A2
Influenza A virus (strain A/Udorn/307/1972 H3N2)
NS1_I72A3
Influenza A virus (strain A/Memphis/102/1972 H3N2)
NS1_I72A4
Influenza A virus (strain A/Memphis/101/1972 H3N2)
NS1_I72A5
Influenza A virus (strain A/Shearwater/Australia/1972 H6N5)
NS1_I72A6
Influenza A virus (strain A/Tern/Turkmenia/18/1972 H3N3)
NS1_I73A4
Influenza A virus (strain A/Equine/London/1416/1973 H7N7)
NS1_I73A5
Influenza A virus (strain A/Port Chalmers/1/1973 H3N2)
NS1_I75A0
Influenza A virus (strain A/Beijing/39/1975 H3N2)
NS1_I76A0
Influenza A virus (strain A/Anas acuta/Primorje/695/1976 H2N3)
NS1_I76A2
Influenza A virus (strain A/Duck/Alberta/60/1976 H12N5)
NS1_I76A5
Influenza A virus (strain A/Mallard/Alberta/88/1976 H3N8)
NS1_I76A6
Influenza A virus (strain A/Memphis/110/1976 H3N2)
NS1_I77A0
Influenza A virus (strain A/Alaska/6/1977 H3N2)
NS1_I77A4
Influenza A virus (strain A/Swine/Colorado/1/1977 H3N2)
NS1_I77A9
Influenza A virus (strain A/Equine/New Market/1/1977 H7N7)
NS1_I77AA
Influenza A virus (strain A/Brazil/11/1978 H1N1)
NS1_I77AB
Influenza A virus (strain A/USSR/90/1977 H1N1)
NS1_I77AF
Influenza A virus (strain A/Gull/Maryland/704/1977 H13N6)
NS1_I77AG
Influenza A virus (strain A/Budgerigar/Hokkaido/1/1977 H4N6)
NS1_I78A1
Influenza A virus (strain A/Mallard/Alberta/827/1978 H8N4)
NS1_I78A3
Influenza A virus (strain A/Mallard/New York/6750/1978 H2N2)
NS1_I78A4
Influenza A virus (strain A/Mallard/New York/6874/1978 H3N2)
NS1_I78A7
Influenza A virus (strain A/Memphis/2/1978 H3N2)
NS1_I78A8
Influenza A virus (strain A/Memphis/18/1978 H3N2)
NS1_I78AA
Influenza A virus (strain A/Pintail/Alberta/268/1978 H6N2)
NS1_I78AC
Influenza A virus (strain A/Turkey/Minnesota/501/1978 H6N8)
NS1_I78AF
Influenza A virus (strain A/Gull/Maryland/1824/1978 H13N6)
NS1_I79A1
Influenza A virus (strain A/Pintail/Alberta/119/1979 H4N6)
NS1_I79A2
Influenza A virus (strain A/Pintail/Alberta/121/1979 H7N8)
NS1_I79A3
Influenza A virus (strain A/Pintail/Alberta/358/1979 H3N6)
NS1_I79A7
Influenza A virus (strain A/Grey teal/Australia/2/1979 H4N4)
NS1_I80A2
Influenza A virus (strain A/Seal/Massachusetts/1/1980 H7N7)
NS1_I80A4
Influenza A virus (strain A/Memphis/4/1980 H3N2)
NS1_I80A6
Influenza A virus (strain A/Duck/Hokkaido/8/1980 H3N8)
NS1_I80A8
Influenza A virus (strain A/Turkey/Minnesota/833/1980 H4N2)
NS1_I80AA
Influenza A virus (strain A/India/6263/1980 H1N1)
NS1_I80AC
Influenza A virus (strain A/Gull/Massachusetts/26/1980 H13N6)
NS1_I80AD
Influenza A virus (strain A/Gull/Minnesota/945/1980 H13N6)
NS1_I80AE
Influenza A virus (strain A/Blue-winged teal/Minnesota/993/1980 H6N6)

Non-structural protein 1 (NS1)

NS1_I82A3
Influenza A virus (strain A/Seal/Massachusetts/133/1982 H4N5)
NS1_I82A8
Influenza A virus (strain A/Turkey/Bethlehem-Glilit/1492-B/1982 H1N1)
NS1_I83A1
Influenza A virus (strain A/Chile/1/1983 H1N1)
NS1_I83A4
Influenza A virus (strain A/Turkey/Ireland/1378/1983 H5N8)
NS1_I83A5
Influenza A virus (strain A/Chicken/Pennsylvania/1/1983 H5N2)
NS1_I83A6
Influenza A virus (strain A/Chicken/Pennsylvania/1370/1983 H5N2)
NS1_I83A8
Influenza A virus (strain A/Hong Kong/5/1983 H3N2)
NS1_I84A2
Influenza A virus (strain A/Whale/Maine/328/1984 H13N2)
NS1_I85A3
Influenza A virus (strain A/Chicken/Victoria/1/1985 H7N7)
NS1_I85A7
Influenza A virus (strain A/Ruddy Turnstone/New Jersey/47/1985 H4N6)
NS1_I86A3
Influenza A virus (strain A/Equine/Tennessee/5/1986 H3N8)
NS1_I87A1
Influenza A virus (strain A/Mallard/Ohio/556/1987 H5N9)
NS1_I88A4
Influenza A virus (strain A/Herring gull/DE/677/1988 H2N8)
NS1_I89A1
Influenza A virus (strain A/Beijing/352/1989 H3N2)
NS1_I89A7
Influenza A virus (strain A/Equine/Jillin/1/1989 H3N8)
NS1_I91A0
Influenza A virus (strain A/Equine/Alaska/1/1991 H3N8)
NS1_I96A2
Influenza A virus (strain A/USA:Memphis/10/1996 H1N1)
NS1_I96A3
Influenza A virus (strain A/China:Nanchang/11/1996 H1N1)
NS1_I97A0
Influenza A virus (strain A/Chicken/Hong Kong/220/1997 H5N1 genotype Gs/Gd)
NS1_I97A1
Influenza A virus (strain A/Hong Kong/156/1997 H5N1 genotype Gs/Gd)
NS1_INCCA
Influenza C virus (strain C/California/1978)
NS1_INCHY
Influenza C virus (strain C/Hyogo/1/1983)
NS1_INCY6
Influenza C virus (strain C/Yamagata/1964)
NS1_ORSVW
Ovine respiratory syncytial virus (strain WSU 83-1578) (ORSV)

Non-structural protein 1 (Non-structural protein 1C)

7 entries

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

Select_allDeselect_all
NS2_BRSVA
Bovine respiratory syncytial virus (strain A51908) (BRS) reference strain
NS2_HRSVB
Human respiratory syncytial virus B (strain B1) reference strain
NS2_MPV15
Murine pneumonia virus (strain 15) (MPV) reference strain
NS2_HRSV
Human respiratory syncytial virus
NS2_HRSV1
Human respiratory syncytial virus B (strain 18537)
NS2_HRSVA
Human respiratory syncytial virus A (strain A2)
NS2_ORSVW
Ovine respiratory syncytial virus (strain WSU 83-1578) (ORSV)

2 entries

Non-structural protein NS-S (NSs)

Select_allDeselect_all
NSS_SFTSV
SFTS phlebovirus (isolate SFTSV/Human/China/HB29/2010) (Severe fever with thrombocytopenia virus) reference strain
NSS_TOSV
Toscana virus (Tos) reference strain

48 entries

Genome polyprotein

Select_allDeselect_all
POLG_EMCVR
Encephalomyocarditis virus (strain Rueckert) (EMCV) reference strain
POLG_HRV8A
Human rhinovirus A serotype 89 (strain 41467-Gallo) (HRV-89) reference strain
POLG_SVV1
Seneca Valley virus (isolate -/United States/SSV-001/2002) (SVV) reference strain
POLG_BOVEV
Bovine enterovirus (strain VG-5-27) (BEV)
POLG_CXA21
Coxsackievirus A21 (strain Coe)
POLG_CXA24
Coxsackievirus A24 (strain EH24/70)
POLG_CXA9
Coxsackievirus A9 (strain Griggs)
POLG_CXB1J
Coxsackievirus B1 (strain Japan)
POLG_CXB2O
Coxsackievirus B2 (strain Ohio-1)
POLG_CXB3N
Coxsackievirus B3 (strain Nancy)
POLG_CXB3W
Coxsackievirus B3 (strain Woodruff)
POLG_CXB4E
Coxsackievirus B4 (strain E2)
POLG_CXB4J
Coxsackievirus B4 (strain JVB / Benschoten / New York/51)
POLG_CXB5P
Coxsackievirus B5 (strain Peterborough / 1954/UK/85)
POLG_CXB6S
Coxsackievirus B6 (strain Schmitt)
POLG_EC01F
Echovirus 1 (strain Human/Egypt/Farouk/1951) (E-1)
POLG_EC05N
Echovirus 5 (strain Noyce)
POLG_EC06C
Echovirus 6 (strain Charles)
POLG_EC09B
Echovirus 9 (strain Barty)
POLG_EC09H
Echovirus 9 (strain Hill)
POLG_EC11G
Echovirus 11 (strain Gregory)
POLG_EC12T
Echovirus 12 (strain Travis)
POLG_EC30B
Echovirus 30 (strain Bastianni)
POLG_EMCV
Encephalomyocarditis virus
POLG_EMCVB
Encephalomyocarditis virus (strain emc-b nondiabetogenic)
POLG_EMCVD
Encephalomyocarditis virus (strain emc-d diabetogenic)
POLG_ENMGO
Mengo encephalomyocarditis virus
POLG_HE701
Human enterovirus 70 (strain J670/71) (EV70) (EV-70)
POLG_HE71
Human enterovirus 71 (EV71) (EV-71)
POLG_HE71B
Human enterovirus 71 (strain USA/BrCr/1970) (EV71) (EV-71)
POLG_HE71M
Human enterovirus 71 (strain 7423/MS/87) (EV71) (EV-71)
POLG_HRV15
Human rhinovirus C (strain C15) (HRV-C15)
POLG_HRV16
Human rhinovirus 16 (HRV-16)
POLG_HRV1A
Human rhinovirus 1A (HRV-1A)
POLG_HRV1B
Human rhinovirus 1B (HRV-1B)
POLG_HRV2
Human rhinovirus 2 (HRV-2)
POLG_HRV3
Human rhinovirus 3 (HRV-3)
POLG_PEV9U
Porcine enterovirus 9 (strain UKG/410/73)
POLG_POL1S
Poliovirus type 1 (strain Sabin)
POLG_POL2L
Poliovirus type 2 (strain Lansing)
POLG_POL2W
Poliovirus type 2 (strain W-2)
POLG_POL32
Poliovirus type 3 (strain 23127)
POLG_POL3L
Poliovirus type 3 (strains P3/Leon/37 and P3/Leon 12A[1]B)
POLG_SVDVH
Swine vesicular disease virus (strain H/3 '76) (SVDV)
POLG_SVDVU
Swine vesicular disease virus (strain UKG/27/72) (SVDV)
POLG_TMEVG
Theiler's murine encephalomyelitis virus (strain GDVII) (TMEV)

1 entry

Non-structural polyprotein pORF1

POLN_HEVCH
Hepatitis E virus genotype 1 (isolate Human/China/HeBei/1987) (HEV) reference strain

3 entries

Accessory factor US11 (Vmw21)

Select_allDeselect_all
RNB_HHV11
Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) reference strain
RNB_HHV2H
Human herpesvirus 2 (strain HG52) (HHV-2) (Human herpes simplex virus 2) reference strain

Probable RNA-binding protein

RNB_HHV1M
Human herpesvirus 1 (strain MP) (HHV-1) (Human herpes simplex virus 1)

RNA-binding protein (Vmw21)

1 entry

Small t antigen (ST) (ST-AG)

ST_POVJC
JC polyomavirus (JCPyV) (JCV)

5 entries

Protein I267L (pI267L)

Select_allDeselect_all
VF267_ASFB7
African swine fever virus (strain Badajoz 1971 Vero-adapted) (Ba71V) (ASFV) reference strain
VF267_ASFK5
African swine fever virus (isolate Pig/Kenya/KEN-50/1950) (ASFV)
VF267_ASFM2
African swine fever virus (isolate Tick/Malawi/Lil 20-1/1983) (ASFV)
VF267_ASFP4
African swine fever virus (isolate Tick/South Africa/Pretoriuskop Pr4/1996) (ASFV)
VF267_ASFWA
African swine fever virus (isolate Warthog/Namibia/Wart80/1980) (ASFV)

1 entry

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

VGLG_HMPVC
Human metapneumovirus (strain CAN97-83) (HMPV) reference strain