Viral Encounters with 2′,5′-Oligoadenylate Synthetase and RNase L during the Interferon Antiviral Response

Silverman, Robert H.

doi:10.1128/jvi.01471-07

Cited by 552 publications

(509 citation statements)

References 124 publications

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“…The primary defect was shown to be the inability to block activation of the IFN-induced 2¢-5¢ OAS/ RNAse L pathway (Min and others 2006). Because 2¢-5¢ OAS has to be activated by dsRNA to activate RNase L (Silverman 2007), this result demonstrated that the primary role of dsRNA binding by the NS1 protein in infected cells is to sequester dsRNA away from 2¢-5¢ OAS. Interestingly, 2¢-5¢ OAS has a very lower affinity for dsRNA (Hartmann and others 2003), indicating that the NS1 protein can effectively compete for dsRNA only with cellular proteins with low affinity for dsRNA.…”

Section: Influenza a Virus Ns1 Proteinmentioning

confidence: 87%

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

Krug

2014

Journal of Interferon & Cytokine Research

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Section: Influenza a Virus Ns1 Proteinmentioning

confidence: 87%

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

Krug

2014

Journal of Interferon & Cytokine Research

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“…It then phosphorylates the eukaryotic translational initiation factor 2 resulting in a translational stop (reviewed in Garcia et al, 2006). OAS also targets dsRNA as a cofactor, which results in the oligomerization of ATP through an unusual 2',5'-phosphodiester linkage that is followed by activation of RNase L. This ribonuclease then degrades cellular and viral RNAs (Silverman, 2007). Mx genes encode for GTPases, which recognize viral nucleocapsids and restrict their localization and the subsequent viral replication within the cell (Haller et al, 2007).…”

mentioning

confidence: 99%

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

Gibbert

Schlaak

Yang

et al. 2013

British J Pharmacology

154

138

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During most viral infections, the immediate host response is characterized by an induction of type I IFN. These cytokines have various biological activities, including anti‐viral, anti‐proliferative and immunomodulatory effects. After induction, they bind to their IFN‐α/β receptor, which leads to downstream signalling resulting in the expression of numerous different IFN‐stimulated genes. These genes encode anti‐viral proteins that directly inhibit viral replication as well as modulate immune function. Thus, the induction of type I IFN is a very powerful tool for the host to fight virus infections. Many viruses evade this response by various strategies like the direct suppression of IFN induction or inhibition of the IFN signalling pathway. Therefore, the therapeutic application of exogenous type I IFN or molecules that induce strong IFN responses should be of great potential for future immunotherapies against viral infections. Type I IFN is currently used as a treatment in chronic hepatitis B and C virus infection, but as yet is not widely utilized for other viral infections. One reason for this restricted clinical use is that type I IFN belongs to a multigene family that includes 13 different IFN‐α subtypes and IFN‐β, whose individual anti‐viral and immunomodulatory properties have so far not been investigated in detail to improve IFN therapy against viral infections in humans. In this review, we summarize the recent achievements in defining the distinct biological functions of type I IFN subtypes in cell culture and in animal models of viral infection as well as their clinical usage in chronic hepatitis virus infections.

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“…Although 4300 ISGs have been identified, only a few ISGs involved in antiviral effects have been defined, 2,3 including dsRNA-activated protein kinase, 2 0 -5 0 oligoadenylate synthetases, ribonuclease L, Mx-GTPase, and ISG15. [4][5][6] The ISG12 family is a group of small proteins (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) that contain a hydrophobic region (80-120 amino acids) referred to as the ISG12 motif. [7][8][9] In silico analysis has identified four ISG12 genes (6-16, ISG12a, ISG12b, and ISG12c) in humans and three (ISG12a, ISG12b1, and ISG12b2) in mice.…”

mentioning

confidence: 99%

Interferon-stimulated gene ISG12b2 is localized to the inner mitochondrial membrane and mediates virus-induced cell death

Lu¹,

Liao

2010

Cell Death Differ

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Interferons (IFNs) are crucial for host defence against viruses. Many IFN-stimulated genes (ISGs) induced by viral infection exert antiviral effects. Microarray analysis of gene expression induced in liver tissues of mice on dengue virus (DENV) infection has led to identification of the ISG gene ISG12b2. ISG12b2 is also dramatically induced on DENV infection of Hepa 1-6 cells (mouse hepatoma cell line). Here, we performed biochemical and functional analyses of ISG12b2. We demonstrate that ISG12b2 is an inner mitochondrial membrane (IMM) protein containing a cleavable mitochondrial targeting sequence and multiple transmembrane segments. Overexpression of ISG12b2 in Hepa 1-6 induced release of cytochrome c from mitochondria, disruption of the mitochondrial membrane potential, and activation of caspase-9, caspase-3, and caspase-8. Treatment of ISG12b2-overexpressing Hepa 1-6 with inhibitors of pan-caspase, caspase-9, or caspase-3, but not caspase-8, reduced apoptotic cell death, suggesting that ISG12b2 activates the intrinsic apoptotic pathway. Of particular interest, we further demonstrated that ISG12b2 formed oligomers, and that ISG12b2 was able to mediate apoptosis through both Bax/Bak-dependent and Bax/Bakindependent pathways. Our study demonstrates that the ISG12b2 is a novel IMM protein induced by IFNs and regulates mitochondria-mediated apoptosis during viral infection. Cell Death and Differentiation (2011) 18, 925-936; doi:10.1038/cdd.2010.160; published online 10 December 2010Type I interferons (IFNs) are the best-known molecules critical for the resistance to viral infection and the regulation of immune response in host defence against viral infection.

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Viral Encounters with 2′,5′-Oligoadenylate Synthetase and RNase L during the Interferon Antiviral Response

Cited by 552 publications

References 124 publications

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

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

IFN‐α subtypes: distinct biological activities in anti‐viral therapy

Interferon-stimulated gene ISG12b2 is localized to the inner mitochondrial membrane and mediates virus-induced cell death

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