Evidence map›Paper›PMID 30779786›Full record

ArticlePLoS pathogens2019

Human IFIT proteins inhibit lytic replication of KSHV: A new feed-forward loop in the innate immune system.

Dajiang Li, Sankar Swaminathan

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

27 citing papers in PubMed, 43 citations in OpenAlex.

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  10. RNF213 modulates γ-herpesvirus infection and reactivation via targeting the viral Replication and Transcription Activator.Proceedings of the National Academy of Sciences of the United States of America · 2023
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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

2 authors at 1 institution in 1 country.

Dajiang LiDivision of Infectious Diseases, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.ORCID 0000-0003-1263-4150
Sankar SwaminathanDivision of Infectious Diseases, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah, United States of America.ORCID 0000-0002-9773-1277
University of Utah · US

Funding

POSTTRANSCRIPTIONAL GENE REGULATION BY EBV SM PROTEINR01CA081133 · NCI · UNIVERSITY OF UTAH · PI SWAMINATHAN, SANKAR · 1999 to 2022
$4.9M
Restriction of Oncogenic Herpesviruses by Host Cell FactorsI01BX002262 · VA · VA SALT LAKE CITY HEALTHCARE SYSTEM · PI SWAMINATHAN, SANKAR · 2015 to 2019
–
BLRD VA I01 BX002262NCI NIH HHS R01 CA081133
6 · The paper itself

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is causally associated with Kaposi's sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman's disease. The IFIT family of proteins inhibits replication of some viruses, but their effects on KSHV lytic replication was unknown. Here we show that KSHV lytic replication induces IFIT expression in epithelial cells. Depletion of IFIT1, IFIT2 and IFIT3 (IFITs) increased infectious KSHV virion production 25-32-fold compared to that in control cells. KSHV lytic gene expression was upregulated broadly with preferential activation of several genes involved in lytic viral replication. Intracellular KSHV genome numbers were also increased by IFIT knockdown, consistent with inhibition of KSHV DNA replication by IFITs. RNA seq demonstrated that IFIT depletion also led to downregulation of IFN β and several interferon-stimulated genes (ISGs), especially OAS proteins. OAS down-regulation led to decreased RNase L activity and slightly increased total RNA yield. IFIT immunoprecipitation also showed that IFIT1 bound to viral mRNAs and cellular capped mRNAs but not to uncapped RNA or trimethylated RNAs, suggesting that IFIT1 may also inhibit viral mRNA expression through direct binding. In summary, IFIT inhibits KSHV lytic replication through positively regulating the IFN β and OAS RNase L pathway to degrade RNA in addition to possibly directly targeting viral mRNAs.

Indexed as

Adaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsCarrier ProteinsDNA ReplicationDown-RegulationEpithelial CellsGene Expression Regulation, ViralHEK293 CellsHerpesvirus 8, HumanHumansImmunity, InnateInterferon-betaIntracellular Signaling Peptides and ProteinsProteinsRNARNA-Binding ProteinsAdaptor Proteins, Signal TransducingApoptosis Regulatory ProteinsCarrier ProteinsIFIT1 protein, humanIFIT2 protein, humanIFIT3 protein, humanInterferon-betaIntracellular Signaling Peptides and ProteinsProteinsRNARNA-Binding ProteinsRNA, Messenger

Identifiers

PMID30779786
PMCPMC6396945
OpenAlexW2917970601

What OpenQuestion holds

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LicenceCC0
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.