Evidence map›Paper›PMID 34797876›Full record

ArticlePLoS pathogens2021

Nuclear dengue virus NS5 antagonizes expression of PAF1-dependent immune response genes.

Marine J Petit, Matthew W Kenaston, Oanh H Pham, Ariana A Nagainis, Adam T Fishburn, Priya S Shah

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

25 citing papers in PubMed, 33 citations in OpenAlex.

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  5. Nonsense-mediated decay controls a negative feedback loop in innate immune sensing.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  6. Altered histone modifications inbioRxiv : the preprint server for biology · 2025
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  7. Bacterial Puppeteering: How the Stealth BacteriumPathogens (Basel, Switzerland) · 2025
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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

6 authors at 1 institution in 1 country.

Marine J PetitDepartment of Microbiology and Molecular Genetics, University of California, Davis, California, United States of America.ORCID 0000-0001-7427-7203
Matthew W KenastonDepartment of Microbiology and Molecular Genetics, University of California, Davis, California, United States of America.ORCID 0000-0001-8820-227X
Oanh H PhamDepartment of Microbiology and Molecular Genetics, University of California, Davis, California, United States of America.
Ariana A NagainisDepartment of Microbiology and Molecular Genetics, University of California, Davis, California, United States of America.
Adam T FishburnDepartment of Microbiology and Molecular Genetics, University of California, Davis, California, United States of America.
Priya S ShahDepartment of Microbiology and Molecular Genetics, University of California, Davis, California, United States of America.ORCID 0000-0001-7518-2839
University of California, Davis · US

Funding

UC Davis MCB T32 Administrative Supplement to Recognize Excellence in Diversity, Equity, Inclusion, and Accessibility (DEIA) MentorshipT32GM007377 · NIGMS · UNIVERSITY OF CALIFORNIA DAVIS · PI CHEDIN, FREDERIC LOUIS · 1985 to 2023
$9.9M
Animal Models of Infectious Diseases Training ProgramT32AI060555 · NIAID · UNIVERSITY OF CALIFORNIA DAVIS · PI MCSORLEY, STEPHEN J · 2004 to 2025
$3.3M
LEICA AOBS SP2 CONFOCAL FOR THE MCB/DBS IMAGING FACILITY: CELL BIOLOGYS10RR019266 · NCRR · UNIVERSITY OF CALIFORNIA DAVIS · PI NUNNARI, JODI M · 2004 to 2004
$496k
Acquisition of Covaris E220 and Sciclone G3 systems for high throughput sequencinS10OD010786 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI COMAI, LUCA · 2012 to 2012
$311k
NCRR NIH HHS S10 RR019266NIAID NIH HHS T32 AI060555NIGMS NIH HHS T32 GM007377NIH HHS S10 OD010786
6 · The paper itself

Abstract

Dengue virus (DENV) disruption of the innate immune response is critical to establish infection. DENV non-structural protein 5 (NS5) plays a central role in this disruption, such as antagonism of STAT2. We recently found that DENV serotype 2 (DENV2) NS5 interacts with Polymerase associated factor 1 complex (PAF1C). The primary members of PAF1C are PAF1, LEO1, CTR9, and CDC73. This nuclear complex is an emerging player in the immune response. It promotes the expression of many genes, including genes related to the antiviral, antimicrobial and inflammatory responses, through close association with the chromatin of these genes. Our previous work demonstrated that NS5 antagonizes PAF1C recruitment to immune response genes. However, it remains unknown if NS5 antagonism of PAF1C is complementary to its antagonism of STAT2. Here, we show that knockout of PAF1 enhances DENV2 infectious virion production. By comparing gene expression profiles in PAF1 and STAT2 knockout cells, we find that PAF1 is necessary to express immune response genes that are STAT2-independent. Finally, we mapped the viral determinants for the NS5-PAF1C protein interaction. We found that NS5 nuclear localization and the C-terminal region of the methyltransferase domain are required for its interaction with PAF1C. Mutation of these regions rescued the expression of PAF1-dependent immune response genes that are antagonized by NS5. In sum, our results support a role for PAF1C in restricting DENV2 replication that NS5 antagonizes through its protein interaction with PAF1C.

Indexed as

MutationProtein Interaction Domains and MotifsA549 CellsCRISPR-Cas SystemsDengueDengue VirusHumansRNA-SeqSTAT2 Transcription FactorSubcellular FractionsTranscription FactorsViral Nonstructural ProteinsNS5 protein, dengue virusPAF1 protein, humanSTAT2 protein, humanSTAT2 Transcription FactorTranscription FactorsViral Nonstructural Proteins

Identifiers

PMID34797876
PMCPMC8641875
OpenAlexW3213821873

What OpenQuestion holds

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LicenceCC BY
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.