Evidence map›Paper›PMID 20861244›Full record

ArticleJournal of virology2010

Proteasome inhibition in vivo promotes survival in a lethal murine model of severe acute respiratory syndrome.

Xue-Zhong Ma, Agata Bartczak, Jianhua Zhang, Ramzi Khattar, Limin Chen, Ming Feng Liu, Aled Edwards, Gary Levy, Ian D McGilvray

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 2 pooled it
1.5field-weighted citation impact, top 17% 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, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.

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  16. COVID-19 Usurps Host Regulatory Networks.Frontiers in pharmacology · 2020
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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

9 authors at 3 institutions in 2 countries.

Xue-Zhong MaMulti-Organ Transplant Program, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.
Agata Bartczak
Jianhua Zhang
Ramzi Khattar
Limin Chen
Ming Feng Liu
Aled Edwards
Gary Levy
Ian D McGilvray
University Health Network · CABuilding Engineering and Science Talent · USUniversity of Toronto · CA

Funding

Canadian Institutes of Health Research 62488Canadian Institutes of Health Research 79561
6 · The paper itself

Abstract

Ubiquitination is a critical regulator of the host immune response to viral infection, and many viruses, including coronaviruses, encode proteins that target the ubiquitination system. To explore the link between coronavirus infection and the ubiquitin system, we asked whether protein degradation by the 26S proteasome plays a role in severe coronavirus infections using a murine model of SARS-like pneumonitis induced by murine hepatitis virus strain 1 (MHV-1). In vitro, the pretreatment of peritoneal macrophages with inhibitors of the proteasome (pyrrolidine dithiocarbamate [PDTC], MG132, and PS-341) markedly inhibited MHV-1 replication at an early step in its replication cycle, as evidenced by inhibition of viral RNA production. Proteasome inhibition also blocked viral cytotoxicity in macrophages, as well as the induction of inflammatory mediators such as IP-10, gamma interferon (IFN-γ), and monocyte chemoattractant protein 1 (MCP-1). In vivo, intranasal inoculation of MHV-1 results in a lethal pneumonitis in A/J mice. Treatment of A/J mice with the proteasome inhibitor PDTC, MG132, or PS-341 led to 40% survival (P < 0.01), with a concomitant improvement of lung histology, reduced pulmonary viral replication, decreased pulmonary STAT phosphorylation, and reduced pulmonary inflammatory cytokine expression. These data demonstrate that inhibition of the cellular proteasome attenuates pneumonitis and cytokine gene expression in vivo by reducing MHV-1 replication and the resulting inflammatory response. The results further suggest that targeting the proteasome may be an effective new treatment for severe coronavirus infections.

Indexed as

AnimalsBlotting, NorthernBlotting, WesternBoronic AcidsBortezomibCoronavirus InfectionsCytokinesDNA PrimersGene Expression RegulationHistological TechniquesLeupeptinsLungMiceMurine hepatitis virusPhosphorylationPneumoniaATP dependent 26S proteasebenzyloxycarbonylleucyl-leucyl-leucine aldehydeBoronic AcidsBortezomibCytokinesDNA PrimersLeupeptinsProlineprolinedithiocarbamateProteasome Endopeptidase ComplexProteasome InhibitorsPyrazinesSTAT Transcription FactorsThiocarbamates

Identifiers

PMID20861244
PMCPMC2976395
OpenAlexW2110110657

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.