Eukaryotic host translation shutoff by virus (kw:KW-1193)
The majority of cellular mRNAs initiate translation through the recruitment of a multisubunit translation initiation complex termed eIF4F, which consists of the cap-binding protein eIF4E, the RNA helicase eIF4A, and the adaptor protein eIF4G. eIF4G binds poly(A)-binding protein (PABP) to mediate 5' -> 3' communication, probably to promote efficient translation of intact correctly processed mRNAs.
eIF4E binding protein 1 (eIF4E-BP1) functions as a translational repressor that limits eIF4E availability and therefore eIF4F complex formation.

Viruses have evolved ways of interacting with the host translational machinery to shutoff host gene expression. This global inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response


All the viruses inducing the shutoff of translation are able to continue to translate at least part of their mRNAs using non-canonical translation: IRES, Ribosome shunting, or VPG initiation. For adenoviridae, polyomaviridae and togaviridae the cellular translation shutoff takes place at the late phase of infection and ensures an optimal production of viral structural proteins.
Under stress conditions such as viral infection some cellular translation can continue when the cap-dependent translation initiation is inhibited. Expression of specific cellular proteins seems to occur through cap-independent mechanisms


Viruses inducing host translation shutoff:
Family | Virus | Viral protein | Shutoff strategy | Viral translation | ref. |
Adenoviridae | Adenovirus | Shutoff protein 100K | Inhibits eIF4G-Mnk1 and prevents EIF4E phosphorylation | Ribosome shunting on late mRNAs |
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Bunyaviridae | Bunyamwera virus | Nucleoprotein | Nuclear retention of PABP | Viral mRNAs non polyadenylated | ![]() |
Caliciviridae | Norovirus Feline calicivirus | Protease 3C Protease |
PABP cleavage | VPg
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Feline calicivirus | Protease | Cleavage of eIF4G1 and eIF4G2 | VPg ![]() |
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Dicistroviridae | Cripavirus | ? | Dissociation of eIF4G and eIF4E | IRES |
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Orthomyxoviridae | Influenza virus | ? | Dephosphorylation of of eIF-4E | eIF-4E independent translation of viral mRNAs |
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Picornaviridae | Poliovirus | Protease 2A | Cleavage of eIF4GI and eIF4GII | IRES |
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Protease 3C | Cleavage of eIF5B | IRES |
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Protease 3C | PABP cleavage | IRES |
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Rhinovirus | Protease 2A | Cleavage of eIF4GI and eIF4GII | IRES |
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Coxsackie virus | Protease 2A | Cleavage of eIF4GI and eIF4GII | IRES |
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Coxsackie virus | Protease 2A,3C | PABP cleavage | IRES |
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Protease 3C | Cleavage of eIF5B | IRES |
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Encephalomyocarditis virus | Protein 2A | ? | IRES |
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? | Dephosphorylation of 4E-BP1 | IRES |
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Foot-and-mouth disease virus | Leader protease | Cleavage of eIF4GI and eIF4GII | IRES |
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Protease 3C | Cleavage of PABP, eIF3a, eIF3b, and eIF4A | IRES |
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Polyomaviridae | SV40 | Small T antigen | Dephosphorylation of 4E-BP1 | IRES |
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Reoviridae | Rotavirus | NSP3 | Interacts with EIF4G and evicts PABP from initiation complexes. Nuclear relocalization of PABP | NSP3 replaces PABP and bind the non polyAdenylated viral mRNAs |
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Rhabdoviridae | Vesicular stomatitis virus | ? | Dephosphorylation of 4E-BP1 | classical |
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Retroviridae | HIV-1 | Protease | Cleavage of eIF4GI and PABP | IRES |
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HTLV-1 | Protease | Cleavage of eIF4GI | IRES |
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Moloney murine leukemia virus | Protease | Cleavage of eIF4GI and eIF4GII | IRES |
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Togaviridae | Rubella virus | Capsid protein | PABP sequestration | classical |
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Sindbis virus | dsRNA leading to PKR-mediated inhibition of eIF2alpha | DLP |
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Coronaviridae | SARS-CoV | Nsp1 | Binding to host 40S subunit | Viral mRNA protected by 5'-end leader sequence |
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Bat-CoV | Nsp1 | - | - |
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TGEV | Nsp1 | - | - |
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Matching UniProtKB/Swiss-Prot entries
(all links/actions below point to uniprot.org website)203 entries grouped by strain
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Human coronavirus HKU1 (isolate N2) (HCoV-HKU1)
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Murine coronavirus (strain JHM) (MHV-JHM) (Murine hepatitis virus)
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Echovirus 12 (strain Travis)
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Echovirus 30 (strain Bastianni)
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Echovirus 5 (strain Noyce)
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Echovirus 6 (strain Charles)
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Echovirus 9 (strain Barty)
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Echovirus 9 (strain Hill)
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Encephalomyocarditis virus
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Encephalomyocarditis virus (strain emc-b nondiabetogenic)
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Encephalomyocarditis virus (strain emc-d diabetogenic)
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Feline calicivirus (strain CFI/68 FIV) (FCV)
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Feline calicivirus (strain F9) (FCV)
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Feline calicivirus (strain Japanese F4) (FCV)
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Human enterovirus 71 (EV71) (EV-71)
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1 entry
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1 entry
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1 entry
Human immunodeficiency virus type 1 group M subtype B (isolate OYI) (HIV-1)
1 entry
Human immunodeficiency virus type 1 group M subtype B (isolate YU-2) (HIV-1)
1 entry
Human immunodeficiency virus type 1 group M subtype D (isolate NDK) (HIV-1)
1 entry
Human immunodeficiency virus type 1 group M subtype D (isolate Z2/CDC-Z34) (HIV-1)
1 entry
Human immunodeficiency virus type 1 group M subtype F2 (isolate MP255) (HIV-1)
1 entry
Human immunodeficiency virus type 1 group M subtype F2 (isolate MP257) (HIV-1)
1 entry
Human immunodeficiency virus type 1 group M subtype G (isolate 92NG083) (HIV-1)
1 entry
Human immunodeficiency virus type 1 group M subtype G (isolate SE6165) (HIV-1)
1 entry
Human immunodeficiency virus type 1 group M subtype H (isolate VI991) (HIV-1)
1 entry
Human immunodeficiency virus type 1 group M subtype J (isolate SE9173) (HIV-1)
1 entry
Human immunodeficiency virus type 1 group M subtype J (isolate SE9280) (HIV-1)
1 entry
Human immunodeficiency virus type 1 group M subtype K (isolate 96CM-MP535) (HIV-1)
1 entry
Human immunodeficiency virus type 1 group M subtype K (isolate 97ZR-EQTB11) (HIV-1)
1 entry
Human immunodeficiency virus type 1 group N (isolate YBF106) (HIV-1)
1 entry
Human immunodeficiency virus type 1 group O (isolate MVP5180) (HIV-1)
1 entry
Human immunodeficiency virus type 2 subtype A (isolate CAM2) (HIV-2)
1 entry
Human immunodeficiency virus type 2 subtype A (isolate D194) (HIV-2)
1 entry
Human immunodeficiency virus type 2 subtype A (isolate Ghana-1) (HIV-2)
1 entry
Human immunodeficiency virus type 2 subtype A (isolate KR) (HIV-2)
1 entry
Human immunodeficiency virus type 2 subtype A (isolate NIH-Z) (HIV-2)
1 entry
Human immunodeficiency virus type 2 subtype A (isolate ROD) (HIV-2)
1 entry
Human immunodeficiency virus type 2 subtype A (isolate SBLISY) (HIV-2)
1 entry
Human immunodeficiency virus type 2 subtype A (isolate ST) (HIV-2)
1 entry
Human immunodeficiency virus type 2 subtype B (isolate D205) (HIV-2)
1 entry
Human immunodeficiency virus type 2 subtype B (isolate EHO) (HIV-2)
1 entry
Human immunodeficiency virus type 2 subtype B (isolate UC1) (HIV-2)
1 entry
Human klassevirus 1 (HKV-1)
1 entry
Human rhinovirus 14 (HRV-14)
1 entry
Human rhinovirus 16 (HRV-16)
1 entry
Human rhinovirus 1A (HRV-1A)
1 entry
Human rhinovirus 1B (HRV-1B)
1 entry
Human rhinovirus 2 (HRV-2)
1 entry
Human rhinovirus 3 (HRV-3)
1 entry
Human rhinovirus C (strain C15) (HRV-C15)
1 entry
Mengo encephalomyocarditis virus
1 entry
Murine leukemia virus (strain BM5 eco)
1 entry
Poliovirus type 1 (strain Sabin)
1 entry
Poliovirus type 2 (strain Lansing)
1 entry
Poliovirus type 2 (strain W-2)
1 entry
Poliovirus type 3 (strain 23127)
1 entry
Poliovirus type 3 (strains P3/Leon/37 and P3/Leon 12A[1]B)
1 entry
Porcine enterovirus 9 (strain UKG/410/73)
1 entry
Radiation murine leukemia virus
1 entry
Simian immunodeficiency virus (isolate F236/smH4) (SIV-sm) (Simian immunodeficiency virus sooty mangabey monkey)
1 entry
Simian immunodeficiency virus (isolate GB1) (SIV-mnd) (Simian immunodeficiency virus mandrill)
1 entry
Simian immunodeficiency virus (isolate Mm142-83) (SIV-mac) (Simian immunodeficiency virus rhesus monkey)
1 entry
Simian immunodeficiency virus (isolate Mm251) (SIV-mac) (Simian immunodeficiency virus rhesus monkey)
1 entry
Simian immunodeficiency virus (isolate PBj14/BCL-3) (SIV-sm) (Simian immunodeficiency virus sooty mangabey monkey)
1 entry
Simian immunodeficiency virus agm.grivet (isolate AGM gr-1) (SIV-agm.gri) (Simian immunodeficiency virus African green monkey grivet)
1 entry
Simian immunodeficiency virus agm.vervet (isolate AGM TYO-1) (SIV-agm.ver) (Simian immunodeficiency virus African green monkey vervet)
1 entry
Simian immunodeficiency virus agm.vervet (isolate AGM155) (SIV-agm.ver) (Simian immunodeficiency virus African green monkey vervet)
1 entry
Simian immunodeficiency virus agm.vervet (isolate AGM3) (SIV-agm.ver) (Simian immunodeficiency virus African green monkey vervet)
1 entry
Swine vesicular disease virus (strain H/3 '76) (SVDV)
1 entry
Swine vesicular disease virus (strain UKG/27/72) (SVDV)
1 entry
Theiler's murine encephalomyelitis virus (strain BeAn 8386) (TMEV)
1 entry
Theiler's murine encephalomyelitis virus (strain DA) (TMEV)
1 entry