Evidence map›Paper›PMID 10438822›Full record

ArticleJournal of virology1999

Functional analysis of human herpesvirus 8-encoded viral interferon regulatory factor 1 and its association with cellular interferon regulatory factors and p300.

L Burýsek, W S Yeow, B Lubyová, M Kellum, S L Schafer, Y Q Huang, P M Pitha

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed
7.0field-weighted citation impact, top 2% 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

112 citing papers in PubMed, 215 citations in OpenAlex.

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  17. Kaposi sarcoma.Nature reviews. Disease primers · 2019
    Review
  18. Review
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52 more citing papers are in PubMed but not listed here.

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

7 authors at 3 institutions in 1 country.

L BurýsekOncology Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
W S Yeow
B Lubyová
M Kellum
S L Schafer
Y Q Huang
P M Pitha
Johns Hopkins Medicine · USJohns Hopkins University · USNew York University · US

Funding

VIRUS/IFN INDUCED SIGNALING PATHWAY IN PATHOGENICITYR01AI019737 · NIAID · JOHNS HOPKINS UNIVERSITY · PI PITHA-ROWE, PAULA M · 1985 to 2006
$1.6M
CRITICAL ROLE OF HHV8 ENCODED IRF IN AIDS LYMPHOMASR01CA076946 · NCI · JOHNS HOPKINS UNIVERSITY · PI PITHA-ROWE, PAULA M · 1998 to 2001
$500k
Role of Transcription Factor IRF-5 in Infected CellsR21AI019737 · NIAID · JOHNS HOPKINS UNIVERSITY · PI PITHA-ROWE, PAULA M · 2001 to 2001
$286k
NCI NIH HHS CA76946NIAID NIH HHS AI19737NIAID NIH HHS R01 AI019737NIAID NIH HHS R21 AI019737
6 · The paper itself

Abstract

Human herpesvirus 8/Kaposi sarcoma-associated virus (HHV-8/KSHV) contains, in addition to genes required for viral replication, a unique set of nonstructural genes which may be part of viral mimicry and contribute to viral replication and pathogenesis in vivo. Among these, HHV-8 encodes four open reading frames (ORFs) that showed homology to the transcription factors of the interferon regulatory factor (IRF) family. The ORF K9, viral IRF 1 (vIRF-1), has been cloned, and it was shown that, when overexpressed, it down modulates the interferon-mediated transcriptional activation of the interferon-stimulated gene 15 (ISG 15) promoter, and the role of vIRF-1 in viral mimicry was implied. However, the molecular mechanism of this effect has not been clarified. Here, we extend this observation and show that vIRF-1 also downregulates the transcriptional activity of IFNA gene promoter in infected cells by interfering with the transactivating activity of cellular IRFs, including IRF-1 and IRF-3. We further show that ectopic expression of vIRF-1 in NIH 3T3 cells confers resistance to tumor necrosis factor alpha-induced apoptosis. While vIRF-1 is unable to bind DNA with the same specificity as cellular IRFs, we demonstrate by in vitro binding assay that it can associate with the family of cellular IRFs, such as IRF-1 and the interferon consensus sequence binding protein. vIRF-1 interaction domain was localized between amino acids (aa) 152 and 243. While no binding between the full-size IRF-3 and vIRF-1 could be detected by the same assay, we show that vIRF-1 also targets the carboxy-terminal region (aa 1623 to 2414) of the transcriptional coactivator p300 which could also bind IRF-3 and IRF-1. These results demonstrate that vIRF-1 can modulate the transcription of the IFNA genes by direct heterodimerization with members of the IRF family, as well as by competitive binding with cellular transcription factors to the carboxy-terminal region of p300.

Indexed as

Repressor Proteins3T3 CellsAnimalsApoptosisBinding SitesDNA-Binding ProteinsE1A-Associated p300 ProteinHerpesvirus 8, HumanHumansInterferon-alphaInterferon Regulatory Factor-1Interferon Regulatory Factor-2Interferon Regulatory Factor-3MiceNuclear ProteinsPhosphoproteinsDNA-Binding ProteinsE1A-Associated p300 ProteinEp300 protein, mouseInterferon-alphaInterferon Regulatory Factor-1Interferon Regulatory Factor-2Interferon Regulatory Factor-3IRF1 protein, humanIrf1 protein, mouseIRF2 protein, humanIrf2 protein, mouseIRF3 protein, humanIrf3 protein, mouseNuclear ProteinsPhosphoproteinsRepressor ProteinsTrans-ActivatorsTranscription Factors

Identifiers

PMID10438822
PMCPMC104259
OpenAlexW2113210730

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.