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

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dc.contributor.authorCheshenko, Natalia
dc.contributor.authorTrepanier, Janie B.
dc.contributor.authorStefanidou, Martha
dc.contributor.authorBuckley, Niall
dc.contributor.authorGonzalez, Pablo
dc.contributor.authorJacobs, William
dc.contributor.authorHerold, Betsy C.
dc.date.accessioned2025-01-24T00:07:17Z
dc.date.available2025-01-24T00:07:17Z
dc.date.issued2013
dc.description.abstractHSV 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 M), 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.Cheshenko, N., Trepanier, J. B., Stefanidou, M., Buckley, N., Gonzalez, P., Jacobs, W., and Herold, B. C. HSV activates Akt to trigger calcium release and promote viral entry: novel candidate target for treatment and suppression.
dc.fuente.origenWOS
dc.identifier.doi10.1096/fj.12-220285
dc.identifier.eissn1530-6860
dc.identifier.issn0892-6638
dc.identifier.urihttps://doi.org/10.1096/fj.12-220285
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/101909
dc.identifier.wosidWOS:000328841000008
dc.issue.numero7
dc.language.isoen
dc.pagina.final2599
dc.pagina.inicio2584
dc.revistaFaseb journal
dc.rightsacceso restringido
dc.subjectglycoprotein B
dc.subjectglycoprotein D
dc.subjectmiltefosine
dc.subjectgenital herpes
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleHSV activates Akt to trigger calcium release and promote viral entry: novel candidate target for treatment and suppression
dc.typeartículo
dc.volumen27
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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