Inhibitory activity for the interferon-induced protein kinase is associated with the reovirus serotype 1 sigma 3 protein.

Imani, Farhad; Jacobs, Bertram L.

doi:10.1073/pnas.85.21.7887

Cited by 183 publications

(128 citation statements)

References 29 publications

(34 reference statements)

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“…Lastly, most viruses studied to date block phosphorylation of eIF-2␣ by encoding proteins which bind double stranded RNA [e.g., E2L of vaccinia (22)(23)(24), 3 protein of Reo and rotaviruses (25)(26)(27)(28), and NS1 protein of influenza (29)], or proteins or RNA that inactivate PKR by binding to it [e.g., vaccinia K3L, Epstein-Barr virus EBERS 1 and 2 (30), adenovirus VA1 RNA (30,31), influenza virus-induced cellular p58 protein (32)], or degrade PKR [poliovirus (33)]. HIV-1 TAR sequence appears to bind to a cellular TAR binding protein and PKR (34)(35)(36).…”

Section: Discussionmentioning

confidence: 99%

The γ ₁ 34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase

Gross

Roizman

1997

Proc. Natl. Acad. Sci. U.S.A.

712

626

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In human cells infected with herpes simplex virus 1 the double-stranded RNA-dependent protein kinase (PKR) is activated but phosphorylation of the ␣ subunit of eukaryotic translation initiation factor 2 (eIF-2) and total shutoff of protein synthesis is observed only in cells infected with ␥ 1 z34.5 ؊ mutants. The carboxyl-terminal 64 aa of ␥ 1 34.5 protein are homologous to the corresponding domain of MyD116, the murine growth arrest and DNA damage gene 34 (GADD34) protein and the two domains are functionally interchangeable in infected cells. This report shows that (i) the carboxyl terminus of MyD116 interacts with protein phosphatase 1␣ in yeast, and both MyD116 and ␥ 1 34.5 interact with protein phosphatase 1␣ in vitro; (ii) protein synthesis in infected cells is strongly inhibited by okadaic acid, a phosphatase 1 inhibitor; and (iii) the ␣ subunit in purified eIF-2 phosphorylated in vitro is specifically dephosphorylated by S10 fractions of wild-type infected cells at a rate 3000 times that of mock-infected cells, whereas the eIF-2␣-P phosphatase activity of ␥ 1 34.5 ؊ virus infected cells is lower than that of mock-infected cells. The eIF-2␣-P phosphatase activities are sensitive to inhibitor 2. In contrast to eIF-2␣-P phosphatase activity, extracts of mock-infected cells exhibit a 2-fold higher phosphatase activity on [ 32 P]phosphorylase than extracts of infected cells. These results indicate that in infected cells, ␥ 1 34.5 interacts with and redirects phosphatase to dephosphorylate eIF-2␣ to enable continued protein synthesis despite the presence of activated PKR. The GADD34 protein may have a similar function in eukaryotic cells. The proposed mechanism for maintenance of protein synthesis in the face of double-stranded RNA accumulation is different from that described for viruses examined to date.

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Section: Discussionmentioning

confidence: 99%

The γ ₁ 34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase

Gross

Roizman

1997

Proc. Natl. Acad. Sci. U.S.A.

712

626

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“…The ds RNA binding of the viral protein seems to be necessary for the kinase inhibitory e ect (Imani and Jacobs, 1988).…”

Section: General Mechanisms Of Viral Disruption Of Ifn Actionsmentioning

confidence: 99%

Role and fate of PML nuclear bodies in response to interferon and viral infections

2001

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Interferons (IFNs) are a family of secreted proteins with antiviral, antiproliferative and immunomodulatory activities. The di erent biological actions of IFN are believed to be mediated by the products of speci®cally induced cellular genes in the target cells. The promyelocytic leukaemia (PML) protein localizes both in the nucleoplasm and in matrix-associated multi-protein complexes known as nuclear bodies (NBs). PML is essential for the proper formation and the integrity of the NBs. Modi®cation of PML by the Small Ubiquitin MOdi®er (SUMO) was shown to be required for its localization in NBs. The number and the intensity of PML NBs increase in response to interferon (IFN). Inactivation of the IFN-induced PML gene by its fusion to retinoic acid receptor alpha alters the normal localization of PML from the punctuate nuclear patterns of NBs to microdispersed tiny dots and results in uncontrolled growth in Acute Promyelocytic Leukaemia. The NBs-associated proteins, PML, Sp100, Sp140, Sp110, ISG20 and PA28 are induced by IFN suggesting that nuclear bodies could play a role in IFN response. Although the function of PML NBs is still unclear, some results indicate that they may represent preferential targets for viral infections and that PML could play a role in the mechanism of the antiviral action of IFNs. Viruses, which require the cellular machinery for their replication, have evolved di erent ways to counteract the action of IFN by inhibiting IFN signalling, by blocking the activities of speci®c antiviral mediators or by altering PML expression and/or localization on nuclear bodies. Oncogene (2001) 20, 7274 ± 7286.

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“…As one countermeasure against these dsRNA-activated antiviral responses, several animal viruses encode proteins that bind dsRNA. These viruses include both DNA viruses (vaccinia virus) (Chang and Jacobs 1993) and RNA viruses (influenza viruses, reoviruses, and Ebola viruses [EBOVs]) (Imani and Jacobs 1988;Hatada and Fukuda 1992;Lu and others 1995;Chien and others 1997;Liu and others 1997;Basler and others 2003;Hartman and others 2004;Cardenas and others 2006). In this study, the focus will be on the structure and function of the dsRNA-binding proteins encoded by 2 RNA viruses, influenza viruses and EBOVs.…”

mentioning

confidence: 99%

Viral Proteins That Bind Double-Stranded RNA: Countermeasures Against Host Antiviral Responses

Krug

2014

Journal of Interferon & Cytokine Research

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Inhibitory activity for the interferon-induced protein kinase is associated with the reovirus serotype 1 sigma 3 protein.

Cited by 183 publications

References 29 publications

The γ ₁ 34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase

The γ ₁ 34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase

Role and fate of PML nuclear bodies in response to interferon and viral infections

Viral Proteins That Bind Double-Stranded RNA: Countermeasures Against Host Antiviral Responses

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Inhibitory activity for the interferon-induced protein kinase is associated with the reovirus serotype 1 sigma 3 protein.

Cited by 183 publications

References 29 publications

The γ 1 34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase

The γ 1 34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase

Role and fate of PML nuclear bodies in response to interferon and viral infections

Viral Proteins That Bind Double-Stranded RNA: Countermeasures Against Host Antiviral Responses

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Product

Resources

About

The γ ₁ 34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase

The γ ₁ 34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase