Publication:
Influence of glutathione availability on cell damage induced by human immunodeficiency virus type 1 viral protein R

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dc.contributor.authorMonroy, Noemi
dc.contributor.authorHerrero, Laura
dc.contributor.authorCarrasco, Luis
dc.contributor.authorGonzalez Portal, Maria Eugenia
dc.contributor.funderInstituto de Salud Carlos III
dc.date.accessioned2019-06-17T11:16:49Z
dc.date.available2019-06-17T11:16:49Z
dc.date.issued2016-02-02
dc.description.abstractThe human immunodeficiency virus type 1 (HIV-1) encodes for accessory viral protein R (Vpr), which arrests the cell cycle of host cells at G2 and causes mitochondrial dysfunction and alterations in glycolysis. High-level expression of Vpr protein correlates with increased viral production and disease progression. Vpr causes structural and functional injury in many types of eukaryotic cells, whether or not they are permissive for viral replication; among them is the budding yeast Saccharomyces cerevisiae. We hypothesized that the dramatic Vpr-induced injuries in yeast could be prevented by strengthening their redox response capacity. We show that exogenous addition of glutathione (GSH) or its prodrug, N-acetylcysteine (NAC), protected budding yeasts from Vpr-induced cytopathic effects. Moreover, addition of adenosine triphosphate (ATP) to growing cultures of Vpr-producing yeast returned cellular growth to control levels, whereas the addition dehydroascorbic acid (DHA) had only a minor protective effect. The diminished protein levels of Cox2p and Cox4p in wild typeVpr-producing yeasts together with the acute sensitivity of petite yeasts to Vpr activity may have been caused by low intracellular ATP levels. As a consequence of this energy deficit, eukaryotic cells would be unable to synthetize adequate supplies of GSH or to signal the mitochondrial retrograde response. Our findings strongly suggest that the cytopathogenic effect of Vpr protein in eukaryotic cells can be prevented by increasing intracellular antioxidant stores or, alternatively, supplying external ATP. Furthermore, these results support a potentially promising future for S. cerevisiae expression as a modality to search for Vpr-targeted inhibitors.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipThis study was supported by Grant PI08/0912 from Acción Estratégica en Salud and by Programa Intramural de Formación from Instituto de Salud Carlos III.es_ES
dc.format.page123es_ES
dc.format.volume213es_ES
dc.identifier.citationVirus Res. 2016; 213: 116-123es_ES
dc.identifier.doi10.1016/j.virusres.2015.11.017es_ES
dc.identifier.e-issn1872-7492es_ES
dc.identifier.issn0168-1702es_ES
dc.identifier.journalVirus Researches_ES
dc.identifier.pubmedID26597719es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7781
dc.language.isoenges_ES
dc.publisherElsevieres_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI08/0912es_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.virusres.2015.11.017es_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectHIV-1es_ES
dc.subjectHeterologous expressiones_ES
dc.subjectOxidative stresses_ES
dc.subjectPhenotypic analysises_ES
dc.subjectTherapeutic targetes_ES
dc.subjectVpres_ES
dc.subject.meshAdenosine Triphosphatees_ES
dc.subject.meshGlutathionees_ES
dc.subject.meshSaccharomycetaleses_ES
dc.subject.meshvpr Gene Products, Human Immunodeficiency Viruses_ES
dc.subject.meshOxidative Stresses_ES
dc.subject.meshModels, Biologicales_ES
dc.titleInfluence of glutathione availability on cell damage induced by human immunodeficiency virus type 1 viral protein Res_ES
dc.typeresearch articlees_ES
dc.type.hasVersionAMes_ES
dspace.entity.typePublication
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