Evidence map›Paper›PMID 26355087›Full record

ArticleJournal of virology2015

Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 1 Interacts with a Member of the Interferon-Stimulated Gene 15 Pathway.

Sarah R Jacobs, Charles M Stopford, John A West, Christopher L Bennett, Louise Giffin, Blossom Damania

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.4field-weighted citation impact, top 9% 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

42 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
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  8. ISG15: A link between innate immune signaling, DNA replication, and genome stability.BioEssays : news and reviews in molecular, cellular and developmental biology · 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

6 authors at 1 institution in 1 country.

Sarah R JacobsLineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Charles M StopfordLineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
John A WestLineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Christopher L BennettLineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Louise GiffinLineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Blossom DamaniaLineberger Comprehensive Cancer Center and Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA damania@med.unc.edu.
University of North Carolina at Chapel Hill · US

Funding

Integrated Training in Cancer Model SystemsT32CA009156 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DER, CHANNING J. · 1985 to 2020
$19.7M
Proteomics Pathway DiscoveryU19AI109965 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DUNCAN, JOSEPH A · 2014 to 2018
$14.9M
Study of Novel HHV8/KSHV Encoded GenesU19AI107810 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DITTMER, DIRK P · 2013 to 2017
$10.6M
ART Modulation of Viral Pathogenesis in Oral EpitheliaR01DE018304 · NIDCR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DITTMER, DIRK P · 2007 to 2025
$6.9M
INFECTIOUS DISEASE PATHOGENESIS TRAININGT32AI007151 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JULIANO, JONATHAN J · 1985 to 2024
$5.5M
Innate Immunity and KSHVR01DE018281 · NIDCR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAMANIA, BLOSSOM A · 2007 to 2016
$3.5M
Targeting the epigenome of gammaherpesviruses in oral diseaseR01DE023946 · NIDCR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DAMANIA, BLOSSOM A, DITTMER, DIRK P · 2013 to 2017
$2.3M
NCI NIH HHS 5T32-CA09156NCI NIH HHS T32 CA009156NIAID NIH HHS 5T32-AI007151NIAID NIH HHS AI109965NIAID NIH HHS T32 AI007151NIAID NIH HHS U19 AI107810NIAID NIH HHS U19 AI109965NIDCR NIH HHS R01 DE018281NIDCR NIH HHS R01 DE018304NIDCR NIH HHS R01 DE023946
6 · The paper itself

Abstract

unlabelledKaposi's sarcoma-associated herpesvirus (KSHV) is a gammaherpesvirus known to establish lifelong latency in the human host. We and others have previously shown that three KSHV homologs of cellular interferon regulatory factors (IRFs), known as viral IRFs (vIRFs), participate in evasion of the host interferon (IFN) response. We report that vIRF1 interacts with the cellular interferon-stimulated gene 15 (ISG15) E3 ligase, HERC5, in the context of Toll-like receptor 3 (TLR3) activation and IFN induction. The ISG15 protein is covalently conjugated to target proteins upon activation of the interferon response. Interaction between vIRF1 and HERC5 was confirmed by immunoprecipitation, and the region between amino acids 224 and 349 of vIRF1 was required for interaction with HERC5. We further report that expression of vIRF1 in the context of TLR3 activation results in decreased ISG15 conjugation of proteins. Specifically, TLR3-induced ISG15 conjugation and protein levels of cellular IRF3, a known ISG15 target, were decreased in the presence of vIRF1 compared to the control. vIRF1 itself was also identified as a target of ISG15 conjugation. KSHV-infected cells exhibited increased ISG15 conjugation upon reactivation from latency in coordination with increased IFN. Furthermore, knockdown of ISG15 in latently infected cells resulted in a higher level of KSHV reactivation and an increase in infectious virus. These data suggest that the KSHV vIRF1 protein affects ISG15 conjugation and interferon responses and may contribute to effective KSHV replication. IMPORTANCE: The KSHV vIRF1 protein can inhibit interferon activation in response to viral infection. We identified a cellular protein named HERC5, which is the major ligase for ISG15, as a vIRF1 binding partner. vIRF1 association with HERC5 altered ISG15 modification of cellular proteins, and knockdown of ISG15 augmented reactivation of KSHV from latency.

Indexed as

Virus ActivationAmino Acid SequenceCytokinesEnzyme ActivationHEK293 CellsHerpesvirus 8, HumanHumansInterferon Regulatory FactorsIntracellular Signaling Peptides and ProteinsRNA InterferenceRNA, Small InterferingToll-Like Receptor 3Ubiquitin-Protein LigasesUbiquitinsViral ProteinsVirus LatencyCytokinesHERC5 protein, humanInterferon Regulatory FactorsIntracellular Signaling Peptides and ProteinsISG15 protein, humanRNA, Small InterferingTLR3 protein, humanToll-Like Receptor 3Ubiquitin-Protein LigasesUbiquitinsviral interferon regulatory factorsViral Proteins

Identifiers

PMID26355087
PMCPMC4645652
OpenAlexW1860224105

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.