Evidence map›Paper›PMID 24516381›Full record

ArticlePLoS pathogens2014

The master regulator of the cellular stress response (HSF1) is critical for orthopoxvirus infection.

Claire Marie Filone, Ignacio S Caballero, Ken Dower, Marc L Mendillo, Glenn S Cowley, Sandro Santagata, Daniel K Rozelle, Judy Yen, Kathleen H Rubins, Nir Hacohen and 3 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

33 citing papers in PubMed, 55 citations in OpenAlex.

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  10. An HSF1-JMJD6-HSP feedback circuit promotes cell adaptation to proteotoxic stress.Proceedings of the National Academy of Sciences of the United States of America · 2024
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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

13 authors at 4 institutions in 1 country.

Claire Marie FiloneDepartment of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America ; United States Army Medical Research Institute of Infectious Diseases, Virology Division, Fort Detrick, Maryland, United States of America.
Ignacio S CaballeroDepartment of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Ken DowerDepartment of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Marc L MendilloWhitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America.
Glenn S CowleyThe Broad Institute, Cambridge Massachusetts, United States of America.
Sandro SantagataWhitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America.
Daniel K RozelleDepartment of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Judy YenDepartment of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Kathleen H RubinsWhitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America.
Nir HacohenThe Broad Institute, Cambridge Massachusetts, United States of America.
David E RootThe Broad Institute, Cambridge Massachusetts, United States of America.
Lisa E HensleyUnited States Army Medical Research Institute of Infectious Diseases, Virology Division, Fort Detrick, Maryland, United States of America.
John ConnorDepartment of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
Boston University · USBroad Institute · USWhitehead Institute for Biomedical Research · USUnited States Army Medical Research Institute of Infectious Diseases · US

Funding

Stage-Specific Inhibitors of OrthopoxvirusesR03MH094169 · NIMH · BOSTON UNIVERSITY MEDICAL CAMPUS · PI CONNOR, JOHN H · 2011 to 2012
$82k
NIMH NIH HHS R03 MH094169NIMH NIH HHS R03 MH094169-01
6 · The paper itself

Abstract

The genus Orthopoxviridae contains a diverse group of human pathogens including monkeypox, smallpox and vaccinia. These viruses are presumed to be less dependent on host functions than other DNA viruses because they have large genomes and replicate in the cytoplasm, but a detailed understanding of the host factors required by orthopoxviruses is lacking. To address this topic, we performed an unbiased, genome-wide pooled RNAi screen targeting over 17,000 human genes to identify the host factors that support orthopoxvirus infection. We used secondary and tertiary assays to validate our screen results. One of the strongest hits was heat shock factor 1 (HSF1), the ancient master regulator of the cytoprotective heat-shock response. In investigating the behavior of HSF1 during vaccinia infection, we found that HSF1 was phosphorylated, translocated to the nucleus, and increased transcription of HSF1 target genes. Activation of HSF1 was supportive for virus replication, as RNAi knockdown and HSF1 small molecule inhibition prevented orthopoxvirus infection. Consistent with its role as a transcriptional activator, inhibition of several HSF1 targets also blocked vaccinia virus replication. These data show that orthopoxviruses co-opt host transcriptional responses for their own benefit, thereby effectively extending their functional genome to include genes residing within the host DNA. The dependence on HSF1 and its chaperone network offers multiple opportunities for antiviral drug development.

Indexed as

OrthopoxvirusCell LineDNA-Binding ProteinsFluorescent Antibody TechniqueHeat Shock Transcription FactorsHost-Parasite InteractionsHumansImmunoblottingPoxviridae InfectionsReverse Transcriptase Polymerase Chain ReactionTranscription FactorsVirus ReplicationDNA-Binding ProteinsHeat Shock Transcription FactorsHSF1 protein, humanTranscription Factors

Identifiers

PMID24516381
PMCPMC3916389
OpenAlexW2010159688

What OpenQuestion holds

Textmetadata
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.