Evidence map›Paper›PMID 23507869›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2013

HSV activates Akt to trigger calcium release and promote viral entry: novel candidate target for treatment and suppression.

Natalia Cheshenko, Janie B Trepanier, Martha Stefanidou, Niall Buckley, Pablo Gonzalez, William Jacobs, Betsy C Herold

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

70 citing papers in PubMed, 101 citations in OpenAlex.

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  17. Viral MicroRNAs in Herpes Simplex Virus 1 Pathobiology.Current pharmaceutical design · 2024
    Review
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10 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Natalia CheshenkoDepartment of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA.
Janie B Trepanier
Martha Stefanidou
Niall Buckley
Pablo Gonzalez
William Jacobs
Betsy C Herold
Albert Einstein College of Medicine · USHoward Hughes Medical Institute · US

Funding

Immunology/Pathology CoreP30AI051519 · NIAID · YESHIVA UNIVERSITY · PI GOLDSTEIN, HARRIS · 2003 to 2013
$18.6M
Role of Calcium Signaling in HSV-2 InvasionR01AI061679 · NIAID · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI HEROLD, BETSY C. · 2005 to 2009
$1.8M
Role of Calcium Signaling in HSV-2 InvasionR56AI061679 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI HEROLD, BETSY C. · 2010 to 2010
$408k
Howard Hughes Medical InstituteNIAID NIH HHS AI-061679NIAID NIH HHS AI-51519NIAID NIH HHS P30 AI051519NIAID NIH HHS R01 AI061679NIAID NIH HHS R56 AI061679
6 · The paper itself

Abstract

HSV triggers intracellular calcium release to promote viral entry. We hypothesized that Akt signaling induces the calcium responses and contributes to HSV entry. Exposure of human cervical and primary genital tract epithelial, neuronal, or keratinocyte cells to HSV serotype 2 resulted in rapid phosphorylation of Akt. Silencing of Akt with small interfering RNA prevented the calcium responses, blocked viral entry, and inhibited plaque formation by 90% compared to control siRNA. Susceptibility to infection was partially restored if Akt was reintroduced into silenced cells with an Akt-expressing plasmid. HSV-2 variants deleted in glycoproteins B or D failed to induce Akt phosphorylation, and coimmunoprecipitation studies indicated that Akt interacts with glycoprotein B. Cell-surface expression of Akt was rapidly induced in response to HSV exposure. Miltefosine (50 μM), a licensed drug that blocks Akt phosphorylation, inhibited HSV-induced calcium release, viral entry, and plaque formation following infection with acyclovir-sensitive and resistant clinical isolates. Miltefosine blocked amplification of HSV from explanted ganglia to epithelial cells; viral yields were significantly less in miltefosine compared to control-treated cocultures (P<0.01). Together, these findings identify a novel role for Akt in viral entry, link Akt and calcium signaling, and suggest a new target for HSV treatment and suppression.

Indexed as

Virus InternalizationAnimalsAntineoplastic AgentsBlotting, WesternCalciumCell LineCell Line, TumorCells, CulturedChlorocebus aethiopsEpithelial CellsFemaleGlycoproteinsHerpesvirus 2, HumanHost-Pathogen InteractionsHumansKeratinocytesAntineoplastic AgentsCalciumGlycoproteinsmiltefosinePhosphorylcholineProto-Oncogene Proteins c-aktViral Proteinsgenital herpesglycoprotein Bglycoprotein Dmiltefosine

Identifiers

PMID23507869
PMCPMC3688744
OpenAlexW2117191987

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.