Evidence map›Paper›PMID 15727684›Full record

ArticleVirology journal2005

Synergistic inhibition of human cytomegalovirus replication by interferon-alpha/beta and interferon-gamma.

Bruno Sainz, Heather L LaMarca, Robert F Garry, Cindy A Morris

Open access · goldAbstract read
In one paragraph

Article in Virology journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.0field-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

47 citing papers in PubMed, 78 citations in OpenAlex.

  1. Article
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  3. Phospholipid scramblase 1: a frontline defense against viral infections.Frontiers in cellular and infection microbiology · 2025
    Review
  4. Article
  5. Anti-Interferon-γ Therapy for Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024
    Review
  6. Article
  7. Article
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  15. 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.

Bruno SainzDepartment of Microbiology and Immunology, Program in Molecular Pathogenesis and Immunity, Tulane University Health Sciences Center, 1430 Tulane Avenue, SL-38, New Orleans, LA 70112, USA. bsainz@scripps.edu
Heather L LaMarca
Robert F Garry
Cindy A Morris
Tulane University · US

Funding

Primate pilot study: coincident AIDS/relapsing malariaR01RR018229 · NCRR · TULANE UNIVERSITY OF LOUISIANA · PI COGSWELL, FRANK B. · 2003 to 2006
$1.0M
Rapid screen for Ebola virus membrane interactions/drugsR01AI054626 · NIAID · TULANE UNIVERSITY OF LOUISIANA · PI GARRY, ROBERT F · 2003 to 2005
$780k
Rapid screen for HIV TM membrane interactions/drugsR21AI054238 · NIAID · TULANE UNIVERSITY OF LOUISIANA · PI GARRY, ROBERT F · 2003 to 2004
$446k
Novel 3-D Model of Placental Cytomegalovirus InfectionR03HD045768 · NICHD · TULANE UNIVERSITY OF LOUISIANA · PI MORRIS, CINDY ANNE · 2004 to 2006
$223k
NCI NIH HHS CA08921NCRR NIH HHS R01 RR018229NCRR NIH HHS RR018229NIAID NIH HHS AI054238NIAID NIH HHS AI0543818NIAID NIH HHS AI054626NIAID NIH HHS R01 AI054626NIAID NIH HHS R21 AI054238NICHD NIH HHS HD045768NICHD NIH HHS R03 HD045768
6 · The paper itself

Abstract

backgroundRecent studies have shown that gamma interferon (IFN-gamma) synergizes with the innate IFNs (IFN-alpha and IFN-beta) to inhibit herpes simplex virus type 1 (HSV-1) replication in vitro. To determine whether this phenomenon is shared by other herpesviruses, we investigated the effects of IFNs on human cytomegalovirus (HCMV) replication.

resultsWe have found that as with HSV-1, IFN-gamma synergizes with the innate IFNs (IFN-alpha/beta) to potently inhibit HCMV replication in vitro. While pre-treatment of human foreskin fibroblasts (HFFs) with IFN-alpha, IFN-beta or IFN-gamma alone inhibited HCMV plaque formation by approximately 30 to 40-fold, treatment with IFN-alpha and IFN-gamma or IFN-beta and IFN-gamma inhibited HCMV plaque formation by 163- and 662-fold, respectively. The generation of isobole plots verified that the observed inhibition of HCMV plaque formation and replication in HFFs by IFN-alpha/beta and IFN-gamma was a synergistic interaction. Additionally, real-time PCR analyses of the HCMV immediate early (IE) genes (IE1 and IE2) revealed that IE mRNA expression was profoundly decreased in cells stimulated with IFN-alpha/beta and IFN-gamma (approximately 5-11-fold) as compared to vehicle-treated cells. Furthermore, decreased IE mRNA expression was accompanied by a decrease in IE protein expression, as demonstrated by western blotting and immunofluorescence.

conclusionThese findings suggest that IFN-alpha/beta and IFN-gamma synergistically inhibit HCMV replication through a mechanism that may involve the regulation of IE gene expression. We hypothesize that IFN-gamma produced by activated cells of the adaptive immune response may potentially synergize with endogenous type I IFNs to inhibit HCMV dissemination in vivo.

Indexed as

Antiviral AgentsCells, CulturedCytomegalovirusDrug SynergismFibroblastsGene Expression Regulation, ViralHumansInterferon-alphaInterferon-betaInterferon-gammaRNA, MessengerViral Plaque AssayVirus ReplicationAntiviral AgentsInterferon-alphaInterferon-betaInterferon-gammaRNA, Messenger

Identifiers

PMID15727684
PMCPMC554982
OpenAlexW2105340645

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.