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Special Issue "Viruses and the OAS-RNase L Pathway"

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A special issue of Viruses (ISSN 1999-4915).

Deadline for manuscript submissions: closed (30 September 2019) | Viewed by 13104

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Prof. Dr. Susan Weiss

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Guest Editor

Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
Interests: coronavirus pathogenesis; murine coronavirus; human respiratory coronaviruses; MERS-CoV; SARS-CoV-2; common CoVs; viral antagonism of innate immunity; OAS/RNase L; endogenous dsRNA induced pathogenesis; Zika virus

Prof. Dr. Robert H. Silverman
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Guest Editor

Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

Special Issue Information

Dear Colleagues,

OAS-RNase L is a potent interferon-regulated antiviral pathway that severely limits the pathogenesis of many different types of viruses. Upon sensing viral (non-self) dsRNA, OASs produce 2’,5’-oligoadenylates (2-5A) that bind to and cause the activation of RNase L. RNase L then cleaves both the host and viral single-stranded RNA, thereby limiting protein production, virus replication and spread, and causing apoptosis. Recent and exciting advances emphasize the importance of OAS-RNase L in antiviral innate immunity. Some of these studies reveal how viruses evolved many strategies to antagonize OAS-RNase L, including sequestering dsRNA from OAS, degrading 2-5A by viral- or host-encoded enzymes or directly inhibiting RNase L. Other studies extend beyond the antiviral state into cellular responses to host (self) dsRNA induced by genetic or epigenetic events. This unique and first-of-its-kind issue on OAS-RNase L will contribute to our understanding of how this remarkable innate immune pathway impacts human health in the context of viral and genetic diseases and cancer.

Prof. Dr. Susan Weiss
Prof. Dr. Robert H. Silverman
Guest Editors

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Keywords

Ribonuclease L
oligoadenylate synthetase
2’,5’-oligoadenylates
viral antagonists
phosphodiesterases
endogenous dsRNA
antiviral pathways

Published Papers (4 papers)

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Research

11 pages, 2908 KiB

Open AccessCommunication

ABCE1 Acts as a Positive Regulator of Exogenous RNA Decay

and

Viruses 2020, 12(2), 174; https://doi.org/10.3390/v12020174 - 04 Feb 2020

Cited by 3 | Viewed by 2962

Abstract

The 2′-5′-oligoadenylate synthetase (OAS)/RNase L system protects hosts against pathogenic viruses through cleavage of the exogenous single-stranded RNA. In this system, an evolutionally conserved RNA quality control factor Dom34 (known as Pelota (Pelo) in higher eukaryotes) forms a surveillance complex with RNase L to recognize and eliminate the exogenous RNA in a manner dependent on translation. Here, we newly identified that ATP-binding cassette sub-family E member 1 (ABCE1), which is also known as RNase L inhibitor (RLI), is involved in the regulation of exogenous RNA decay. ABCE1 directly binds to form a complex with RNase L and accelerates RNase L dimer formation in the absence of 2′-5′ oligoadenylates (2-5A). Depletion of ABCE1 represses 2-5A-induced RNase L activation and stabilizes exogenous RNA to a level comparable to that seen in RNase L depletion. The increased half-life of the RNA by the single depletion of either protein is not significantly affected by the double depletion of both proteins, suggesting that RNase L and ABCE1 act together to eliminate exogenous RNA. Our results indicate that ABCE1 functions as a positive regulator of exogenous RNA decay rather than an inhibitor of RNase L. Full article

(This article belongs to the Special Issue Viruses and the OAS-RNase L Pathway)

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16 pages, 1894 KiB

Open AccessArticle

Characteristics of Human OAS1 Isoform Proteins

Han Di

Husni Elbahesh

and

Margo A. Brinton

Viruses 2020, 12(2), 152; https://doi.org/10.3390/v12020152 - 29 Jan 2020

Cited by 8 | Viewed by 3332

Abstract

The human OAS1 (hOAS1) gene produces multiple possible isoforms due to alternative splicing events and sequence variation among individuals, some of which affect splicing. The unique C-terminal sequences of the hOAS1 isoforms could differentially affect synthetase activity, protein stability, protein partner interactions and/or cellular localization. Recombinant p41, p42, p44, p46, p48, p49 and p52 hOAS1 isoform proteins expressed in bacteria were each able to synthesize trimer and higher order 2′-5′ linked oligoadenylates in vitro in response to poly(I:C). The p42, p44, p46, p48 and p52 isoform proteins were each able to induce RNase-mediated rRNA cleavage in response to poly(I:C) when overexpressed in HEK293 cells. The expressed levels of the p42 and p46 isoform proteins were higher than those of the other isoforms, suggesting increased stability in mammalian cells. In a yeast two-hybrid screen, Fibrillin1 (FBN1) was identified as a binding partner for hOAS1 p42 isoform, and Supervillin (SVIL) as a binding partner for the p44 isoform. The p44-SVIL interaction was supported by co-immunoprecipitation data from mammalian cells. The data suggest that the unique C-terminal regions of hOAS1 isoforms may mediate the recruitment of different partners, alternative functional capacities and/or different cellular localization. Full article

(This article belongs to the Special Issue Viruses and the OAS-RNase L Pathway)

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10 pages, 2538 KiB

Open AccessArticle

RNase L Is Involved in Liposaccharide-Induced Lung Inflammation

and

Viruses 2020, 12(1), 73; https://doi.org/10.3390/v12010073 - 07 Jan 2020

Cited by 3 | Viewed by 2293

Abstract

RNase L mediates interferon (IFN) function during viral infection and cell proliferation. Furthermore, the role of RNase L in the regulation of gene expression, cell apoptosis, autophagy, and innate immunity has been well established in the last decade. Tissue distribution reveals that RNase L is highly expressed in the lung and other organs. However, the physiological roles of RNase L in the lung are largely unknown. In this study, we found that polysaccharide (LPS)-induced acute lung injury (ALI) was remarkably intensified in mice deficient in RNase L compared to wild type mice under the same condition. Furthermore, we found that RNase L mediated the TLR4 signaling pathway, and regulated the expression of various pro- and anti-inflammatory genes in the lung tissue and blood. Most importantly, RNase L function in macrophages during LPS stimulation may be independent of the 2-5A system. These findings demonstrate a novel role of RNase L in the immune response via an atypical molecular mechanism. Full article

(This article belongs to the Special Issue Viruses and the OAS-RNase L Pathway)

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19 pages, 3851 KiB

Open AccessArticle

The Cellular Localization of the p42 and p46 Oligoadenylate Synthetase 1 Isoforms and Their Impact on Mitochondrial Respiration

Stig Skrivergaard

Monica Skou Jensen

Tine Breckling Rolander

and

Viruses 2019, 11(12), 1122; https://doi.org/10.3390/v11121122 - 04 Dec 2019

Cited by 8 | Viewed by 3553

Abstract

The importance of the IFN-induced oligoadenylate synthetase (OAS) proteins and the OAS/RNase L pathway in the innate response against viral pathogens is well-established, however the observed differences in anti-viral activity between the human OAS1 p46 and p42 isoforms are not fully understood. The protein expression of these isoforms is determined by the SNP rs10774671, either being an A or a G allele resulting in expression of either the p42 or the p46 isoform. Using fluorescence microscopy and immunoblot analysis of fractionated cell samples, we show here that the CaaX motif is of key importance to the cellular localization. The OAS1 p42 isoform is mainly located in the cytosol, whereas the p46 isoform with a C-terminal CaaX motif is translocated to membranous organelles, like the mitochondria. We furthermore observed differences between p42 and p46 in their effect on mitochondrial physiology using high resolution respirometry and fluorometry. Overexpression of OAS1 p42 and IFN-β treatment of HeLa cells (AA genotype) resulted in significantly increased respiration, which was not seen with p46 overexpression. The difference in subcellular localization and mitochondrial effect of these two OAS1 isoforms might help to explain the anti-viral mechanisms that differentiate these proteins. Full article

(This article belongs to the Special Issue Viruses and the OAS-RNase L Pathway)

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