(2′‐5′)A<sub>n</sub>‐dependent endoribonuclease: Enzyme levels are regulated by IFNβ, IFNγ, and cell culture conditions

Floyd-Smith, Georgia

doi:10.1002/jcb.240380103

Cited by 9 publications

(4 citation statements)

References 25 publications

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“…RNase L is constitutively present in most types of cells (112), although treatment with IFN-␣/␤ enhances RNase L activity in some types of cells (111,182). Subsequent Northern blot analysis established that IFN-␣/␤ increases the steady-state amount of the RNase L transcript in mouse cells by about threefold (450).…”

Section: 5-oligoadenylate Synthetase and Rnase Lmentioning

confidence: 99%

Antiviral Actions of Interferons

2001

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Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of IFNs. Furthermore, advances made while elucidating the IFN system have contributed significantly to our understanding in multiple areas of virology and molecular cell biology, ranging from pathways of signal transduction to the biochemical mechanisms of transcriptional and translational control to the molecular basis of viral pathogenesis. IFNs are approved therapeutics and have moved from the basic research laboratory to the clinic. Among the IFN-induced proteins important in the antiviral actions of IFNs are the RNA-dependent protein kinase (PKR), the 2′,5′-oligoadenylate synthetase (OAS) and RNase L, and the Mx protein GTPases. Double-stranded RNA plays a central role in modulating protein phosphorylation and RNA degradation catalyzed by the IFN-inducible PKR kinase and the 2′-5′-oligoadenylate-dependent RNase L, respectively, and also in RNA editing by the IFN-inducible RNA-specific adenosine deaminase (ADAR1). IFN also induces a form of inducible nitric oxide synthase (iNOS2) and the major histocompatibility complex class I and II proteins, all of which play important roles in immune response to infections. Several additional genes whose expression profiles are altered in response to IFN treatment and virus infection have been identified by microarray analyses. The availability of cDNA and genomic clones for many of the components of the IFN system, including IFN-α, IFN-β, and IFN-γ, their receptors, Jak and Stat and IRF signal transduction components, and proteins such as PKR, 2′,5′-OAS, Mx, and ADAR, whose expression is regulated by IFNs, has permitted the generation of mutant proteins, cells that overexpress different forms of the proteins, and animals in which their expression has been disrupted by targeted gene disruption. The use of these IFN system reagents, both in cell culture and in whole animals, continues to provide important contributions to our understanding of the virus-host interaction and cellular antiviral response

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Section: 5-oligoadenylate Synthetase and Rnase Lmentioning

confidence: 99%

Antiviral Actions of Interferons

2001

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“…The oligoadenylate synthetase (OAS)/RNase L pathway is another of the most extensively characterized. IFNαβ signaling stimulates synthesis of OAS and RNase L (Floyd -Smith, 1988), and once the cell is infected, viral double-stranded RNA (dsRNA) activates OAS to produce 2′5′-linked oligoadenylates (2′5′A). The 2′5′A then activate RNase L to degrade RNA, resulting in translation inhibition and blockade of viral replication.…”

Section: Introductionmentioning

confidence: 99%

Herpes simplex virus type 2-mediated disease is reduced in mice lacking RNase L

Duerst

Morrison

2007

Virology

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RNase L helps mediate the antiviral state induced by type I interferons (IFNalphabeta). Although herpes simplex virus (HSV) encodes inhibitors of the IFNalphabeta-induced antiviral response, the IFNalphabeta system serves the body as a first line of defense against HSV. We investigated whether RNase L limits HSV-2 replication and virulence. RNaseL(-/-) and wild-type C57BL/6 mice were infected intravaginally with HSV-2 strain 333. Although initial replication in the genital epithelium was similar, mice lacking RNase L developed less severe genital and neurologic disease than wild-type mice, survived longer, and contained lower viral titers in the nervous system. CD4(+) T cell infiltration into the genital tract and spinal cord of RNase L(-/-) mice was reduced, suggesting that a restricted inflammatory response may account for reduction in disease. Thus, RNase L does not play a significant role in control of HSV-2 infection in vivo; instead, RNase L may regulate aspects of the inflammatory response that contribute to disease.

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“…We suggested that intracellular constitutive RNase L could be activated by EV71 infection to degraded viral RNA. Previous studies have shown that RNase L is constitutively present in most types of cells ( Floyd-Smith and Denton, 1988 ), and treatment with IFN-α/β enhances RNase L activity in some types of cells ( Jacobsen et al., 1983 ; Floyd-Smith, 1988 ). We next demonstrated that EV71 infection could induce OAS3 but not RNase L expression ( Fig.…”

Section: Discussionmentioning

confidence: 99%