Evidence map›Paper›PMID 31142667›Full record

ArticleJournal of virology2019

Zika Virus Production Is Resistant to RNase L Antiviral Activity.

Jillian N Whelan, Yize Li, Robert H Silverman, Susan R Weiss

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
6.0field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 54 citations in OpenAlex.

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  6. A CRISPR-Cas9 knockout screening identifies IRF2 as a key driver of OAS3/RNase L-mediated RNA decay during viral infection.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  13. The Many Faces of Oligoadenylate Synthetases.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Jillian N WhelanDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia Pennsylvania, USA.
Yize LiDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia Pennsylvania, USA.
Robert H SilvermanDepartment of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Susan R WeissDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia Pennsylvania, USA weisssr@pennmedicine.upenn.edu.ORCID 0000-0002-8155-4528
University of Pennsylvania · USCleveland Clinic Lerner College of Medicine · US

Funding

Control of Viral Pathogenesis by Regulation of 2-5A LevelsR01AI104887 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI SILVERMAN, ROBERT H., WEISS, SUSAN R · 2013 to 2023
$7.6M
TRAINING IN NEUROVIROLOGY AND NEUROIMMUNOLOGYT32NS007180 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI WEISS, SUSAN R · 1985 to 2018
$2.8M
Role of type I interferon signaling in Zika virus infection of the brainR21NS100182 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI WEISS, SUSAN R · 2016 to 2017
$443k
NIAID NIH HHS R01 AI104887NINDS NIH HHS R21 NS100182NINDS NIH HHS T32 NS007180
6 · The paper itself

Abstract

There is currently no knowledge of how the emerging human pathogen Zika virus (ZIKV) interacts with the antiviral endoribonuclease L (RNase L) pathway during infection. Since activation of RNase L during infection typically limits virus production dramatically, we used CRISPR-Cas9 gene editing technology to knockout (KO) targeted host genes involved in the RNase L pathway to evaluate the effects of RNase L on ZIKV infection in human A549 cells. RNase L was activated in response to ZIKV infection, which degraded ZIKV genomic RNA. Surprisingly, despite viral genome reduction, RNase L activity did not reduce ZIKV infectious titers. In contrast, both the flavivirus dengue virus and the alphavirus Sindbis virus replicated to significantly higher titers in RNase L KO cells compared to wild-type (WT) cells. Using MAVS/RNase L double KO cells, we demonstrated that the absence of increased ZIKV production in RNase L KO cells was not due to compensation by enhanced type I interferon transcripts to thus inhibit virus production. Finally, when synthetic double-stranded RNA was detected by OAS3 to induce RNase L antiviral activity prior to ZIKV infection, we observed reduced ZIKV replication factory formation, as well as a 42-fold reduction in virus yield in WT but not RNase L KO cells. This study proposes that ZIKV evades RNase L antiviral activity by generating a viral genome reservoir protected from RNase L cleavage during early infection, allowing for sufficient virus production before RNase L activation is detectable.

Indexed as

Host-Pathogen InteractionsVirus ReplicationCell LineCells, CulturedEndoribonucleasesEnzyme ActivationGenome, ViralHumansInterferonsModels, BiologicalRNA, ViralZika VirusZika Virus Infection2-5A-dependent ribonucleaseEndoribonucleasesInterferonsRNA, Viraldengue virusinnate immunityreplication factoriesRNARNase LSindbis virusviral genomeZika virus

Identifiers

PMID31142667
PMCPMC6675901
OpenAlexW2947623422

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.