Inhibition of host PKR by virus

The protein kinase regulated by RNA, PKR, plays an important function in innate immune response. The N-terminal includes a repeated domain that confers dsRNA-binding activity while the C-terminal confers the kinase activity. The best characterized substrate of PKR is the alpha-subunit of protein synthesis initiator 2 (eIF-2alpha(J02645:9606) ). When phosphorylated by PKR, eIF-2alpha leads to an inhibition of translation. Therefore, PKR is a key factor in the host antiviral response, through inhibition of protein synthesis during viral infection.


Viruses have evolved specific mechanisms to prevent the establishment of an antiviral state by inhibiting key components of the signaling pathway . For instance, several viral proteins antagonists of PKR have been identified, many of which are RNA-binding proteins. Among them, E3L(P21605) and K3L(P18378) from vaccinia and sigma3(P07939) protein from reoviruses. E3L(P21605) was found to inhibit host PKR activity through direct interaction. Hepatitis C virus NS5A(P27958), Herpes simplex 1 US11(P04487), and Kaposi’s sarcoma vIRF-2 protein also interact with and inhibit PKR. Some viruses including HCMV or MCMV alter PKR subcellular localization while others direct PKR to degradation like Rift valley fever virus NSs(P21698:9606) protein.

Matching UniProtKB/Swiss-Prot entries

85 entries grouped by protein (browse by keywords)

Only complete proteome entries are shown (view all 165 entries)

1 entry

G-protein coupled receptor BILF1

BILF1_EBVB9
Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4) reference strain

1 entry

E1B 55 kDa protein (E1B-55K) (E1B protein, large T-antigen) (E1B-495R)

E1B55_ADE02
Human adenovirus C serotype 2 (HAdV-2) (Human adenovirus 2) reference strain

3 entries

Protein E3 (p25)

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E3_VACCW
Vaccinia virus (strain Western Reserve) (VACV) (Vaccinia virus (strain WR)) reference strain
E3_VAR67
Variola virus (isolate Human/India/Ind3/1967) (VARV) (Smallpox virus) reference strain

Protein E3

E3_VACCC
Vaccinia virus (strain Copenhagen) (VACV)

3 entries

mRNA export factor ICP27 homolog (Mta) (ORF57 protein homolog) (Protein SM)

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ICP27_EBVA8
Epstein-Barr virus (strain AG876) (HHV-4) (Human herpesvirus 4) reference strain
ICP27_EBVB9
Epstein-Barr virus (strain B95-8) (HHV-4) (Human herpesvirus 4) reference strain
ICP27_EBVG
Epstein-Barr virus (strain GD1) (HHV-4) (Human herpesvirus 4)

2 entries

Protein IRS1

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IRS1_HCMVA
Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5) reference strain

Protein IRS1 (HQRF1)

IRS1_HCMVM
Human cytomegalovirus (strain Merlin) (HHV-5) (Human herpesvirus 5) reference strain

2 entries

Protein K3

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K3_VACCW
Vaccinia virus (strain Western Reserve) (VACV) (Vaccinia virus (strain WR)) reference strain

Protein K3 (Protein K2)

K3_VACCC
Vaccinia virus (strain Copenhagen) (VACV)

4 entries

Nucleoprotein (Protein N) (Nucleocapsid protein)

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NCAP_BRSVA
Bovine respiratory syncytial virus (strain A51908) (BRS) reference strain
NCAP_HRSVA
Human respiratory syncytial virus A (strain A2) reference strain
NCAP_HRSVB
Human respiratory syncytial virus B (strain B1) reference strain
NCAP_MPV15
Murine pneumonia virus (strain 15) (MPV)

Nucleoprotein (Nucleocapsid protein) (NP) (Protein N)

60 entries

Non-structural protein 1 (NS1) (NS1A)

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NS1_I34A1
Influenza A virus (strain A/Puerto Rico/8/1934 H1N1) reference strain
NS1_I72A5
Influenza A virus (strain A/Shearwater/Australia/1972 H6N5) reference strain
NS1_I78A3
Influenza A virus (strain A/Mallard/New York/6750/1978 H2N2) reference strain
NS1_I80A8
Influenza A virus (strain A/Turkey/Minnesota/833/1980 H4N2) reference strain
NS1_I83A6
Influenza A virus (strain A/Chicken/Pennsylvania/1370/1983 H5N2) reference strain
NS1_I96A0
Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd) reference strain
NS1_INBLE
Influenza B virus (strain B/Lee/1940) reference strain
NS1_I00A0
Influenza A virus (strain A/Duck/Hong Kong/2986.1/2000 H5N1 genotype C)
NS1_I02A0
Influenza A virus (strain A/Chicken/Brescia/1902 H7N7)
NS1_I06A0
Influenza A virus (strain A/Russia:St.Petersburg/8/2006 H1N1)
NS1_I18A0
Influenza A virus (strain A/Brevig Mission/1/1918 H1N1) (Influenza A virus (strain A/South Carolina/1/1918 H1N1))
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_I49A1
Influenza A virus (strain A/Duck/Germany/1949 H10N7)
NS1_I51A0
Influenza A virus (strain A/USA:Albany/12/1951 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_I59A0
Influenza A virus (strain A/Chicken/Scotland/1959 H5N1)
NS1_I61A1
Influenza A virus (strain A/Swine/Wisconsin/1/1961 H1N1)
NS1_I66A1
Influenza A virus (strain A/Turkey/Wisconsin/1/1966 H9N2)
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_I71A1
Influenza A virus (strain A/Memphis/1/1971 H3N2)
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_I73A5
Influenza A virus (strain A/Port Chalmers/1/1973 H3N2)
NS1_I75A0
Influenza A virus (strain A/Beijing/39/1975 H3N2)
NS1_I76A6
Influenza A virus (strain A/Memphis/110/1976 H3N2)
NS1_I77A4
Influenza A virus (strain A/Swine/Colorado/1/1977 H3N2)
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_I78A7
Influenza A virus (strain A/Memphis/2/1978 H3N2)
NS1_I78A8
Influenza A virus (strain A/Memphis/18/1978 H3N2)
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_I80AA
Influenza A virus (strain A/India/6263/1980 H1N1)
NS1_I80AD
Influenza A virus (strain A/Gull/Minnesota/945/1980 H13N6)
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_I83A8
Influenza A virus (strain A/Hong Kong/5/1983 H3N2)
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_I96A2
Influenza A virus (strain A/USA:Memphis/10/1996 H1N1)
NS1_I96A3
Influenza A virus (strain A/China:Nanchang/11/1996 H1N1)
NS1_I97A1
Influenza A virus (strain A/Hong Kong/156/1997 H5N1 genotype Gs/Gd)
NS1_INBSI
Influenza B virus (strain B/Singapore/222/1979)

1 entry

Non-structural protein S (NSs)

NSS_RVFVZ
Rift valley fever virus (strain ZH-548 M12) (RVFV) reference strain

2 entries

Accessory factor US11 (Vmw21)

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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

3 entries

Outer capsid protein sigma-3 (Sigma3)

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SIGM3_REOVD
Reovirus type 3 (strain Dearing) (T3D) (Mammalian orthoreovirus 3) reference strain
SIGM3_REOVL
Reovirus type 1 (strain Lang) (T1L) (Mammalian orthoreovirus 1) reference strain
SIGM3_REOVJ
Reovirus type 2 (strain D5/Jones) (T2J) (Mammalian orthoreovirus 2)

2 entries

Protein HHLF1

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TRS1_HCMVA
Human cytomegalovirus (strain AD169) (HHV-5) (Human herpesvirus 5) reference strain
TRS1_HCMVM
Human cytomegalovirus (strain Merlin) (HHV-5) (Human herpesvirus 5) reference strain

Protein TRS1

1 entry

Viral IRF2-like protein (vIRF-2)

VIRF2_HHV8P
Human herpesvirus 8 type P (isolate GK18) (HHV-8) (Kaposi's sarcoma-associated herpesvirus) reference strain