Evidence map›Paper›PMID 29084250›Full record

ArticlePLoS pathogens2017

KSHV inhibits stress granule formation by viral ORF57 blocking PKR activation.

Nishi R Sharma, Vladimir Majerciak, Michael J Kruhlak, Zhi-Ming Zheng

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing 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

59 citing papers in PubMed, 79 citations in OpenAlex.

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  18. RNA recognition by PKR during DNA virus infection.Journal of medical virology · 2024
    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 1 institution in 1 country.

Nishi R SharmaTumor Virus RNA Biology Section, RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Frederick, Maryland, United States of America.
Vladimir MajerciakTumor Virus RNA Biology Section, RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Frederick, Maryland, United States of America.
Michael J KruhlakExperimental Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
Zhi-Ming ZhengTumor Virus RNA Biology Section, RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, NIH, Frederick, Maryland, United States of America.ORCID http://orcid.org/0000-0001-5547-7912
National Cancer Institute · US

Funding

EIB Microscopy Core FacilityZICBC010915 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI WISNIEWSKI, JAN · 2009 to 2025
$6.1M
6 · The paper itself

Abstract

TIA-1 positive stress granules (SG) represent the storage sites of stalled mRNAs and are often associated with the cellular antiviral response. In this report, we provide evidence that Kaposi's sarcoma-associated herpesvirus (KSHV) overcomes the host antiviral response by inhibition of SG formation via a viral lytic protein ORF57. By immunofluorescence analysis, we found that B lymphocytes with KSHV lytic infection are refractory to SG induction. KSHV ORF57, an essential post-transcriptional regulator of viral gene expression and the production of new viral progeny, inhibits SG formation induced experimentally by arsenite and poly I:C, but not by heat stress. KSHV ORF37 (vSOX) bearing intrinsic endoribonuclease activity also inhibits arsenite-induced SG formation, but KSHV RTA, vIRF-2, ORF45, ORF59 and LANA exert no such function. ORF57 binds both PKR-activating protein (PACT) and protein kinase R (PKR) through their RNA-binding motifs and prevents PACT-PKR interaction in the PKR pathway which inhibits KSHV production. Consistently, knocking down PKR expression significantly promotes KSHV virion production. ORF57 interacts with PKR to inhibit PKR binding dsRNA and its autophosphorylation, leading to inhibition of eIF2α phosphorylation and SG formation. Homologous protein HSV-1 ICP27, but not EBV EB2, resembles KSHV ORF57 in the ability to block the PKR/eIF2α/SG pathway. In addition, KSHV ORF57 inhibits poly I:C-induced TLR3 phosphorylation. Altogether, our data provide the first evidence that KSHV ORF57 plays a role in modulating PKR/eIF2α/SG axis and enhances virus production during virus lytic infection.

Indexed as

Cytoplasmic GranuleseIF-2 KinaseEnzyme ActivationGene Knockdown TechniquesHEK293 CellsHeLa CellsHerpesviridae InfectionsHerpesvirus 8, HumanHumansPoly I-CT-Cell Intracellular Antigen-1Toll-Like Receptor 3Viral Regulatory and Accessory ProteinsVirionEIF2AK2 protein, humaneIF-2 KinaseORF57 protein, human herpesvirus 8Poly I-CT-Cell Intracellular Antigen-1TIA1 protein, humanTLR3 protein, humanToll-Like Receptor 3Viral Regulatory and Accessory Proteins

Identifiers

PMID29084250
PMCPMC5679657
OpenAlexW2766643218

What OpenQuestion holds

Textmetadata
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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.