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June 1, 2014Journal of Interferon & Cytokine ResearchOpen Access

Viral Phosphodiesterases That Antagonize Double-Stranded RNA Signaling to RNase L by Degrading 2-5A

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Key result

Viral proteins such as coronavirus ns2 and rotavirus VP3 antagonize the host interferon antiviral response by functioning as 2',5'-phosphodiesterases that degrade 2-5A, preventing RNase L activation.

Population

Preclinical models including wild-type B6 mice, RNase L -/- mice, and bone marrow-derived macrophages…

Comparison

Viral proteins with 2',5'-phosphodiesterase… vs Mutant viruses lacking PDE activity or wild-type…

Design

Review

Authors

RSRobert H. SilvermanCleveland State UniversitySWSusan R. WeissUniversity of Pennsylvania

Discussion

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Implication

Viral phosphodiesterases may guide antiviral target discovery; leaves open whether RNase L pathway modulation improves outcomes in RNA virus infections.

Structured PICO

P
Population
Preclinical models including wild-type B6 mice, RNase L -/- mice, and bone marrow-derived macrophages (BMM) infected with mouse hepatitis virus (MHV) or rotavirus.
I
Intervention
Viral proteins with 2',5'-phosphodiesterase (PDE) activities (e.g., MHV ns2, rotavirus VP3-CTD) that degrade 2-5A
C
Comparator
Mutant viruses lacking PDE activity (e.g., ns2H126R) or wild-type mice versus RNase L -/- mice
O
Outcome
Viral replication, rRNA degradation, 2-5A accumulation, and pathogenesis (e.g., hepatitis)

Viral 2',5'-phosphodiesterases represent a conserved mechanism by which disparate RNA viruses evade the host OAS/RNase L antiviral pathway.

Cite This Study

Silverman et al. (2014) conducted a review in Viral infections. Viral proteins such as coronavirus ns2 and rotavirus VP3 antagonize the host interferon antiviral response by functioning as 2',5'-phosphodiesterases that degrade 2-5A, preventing RNase L activation.

synapsesocial.com/papers/6a1b066787cea61d1f4c5ce3https://doi.org/10.1089/jir.2014.0007
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Homologous 2′,5′-phosphodiesterases from disparate RNA viruses antagonize antiviral innate immunity2013 · 128 citations
  2. 2A viral RNA competitively inhibits the antiviral endoribonuclease domain of RNase L2008 · 58 citations
  3. 3Coronavirus Gene 7 Counteracts Host Defenses and Modulates Virus Virulence2011 · 138 citations
  4. 4Mouse hepatitis virus ORF 2a is expressed in the cytosol of infected mouse fibroblasts1990 · 20 citations
  5. 5Molecular cloning and characterization of two related and interferon‐induced 56‐kDa and 30‐kDa proteins highly similar to 2′‐5′ oligoadenylate synthetase1998 · 86 citations