2026-06-14T12:13:36Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/77812024-09-27T23:57:31Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Monroy, Noemi
author
Herrero, Laura
author
Carrasco, Luis
author
Gonzalez Portal, Maria Eugenia
funder
Instituto de Salud Carlos III
2019-06-17T11:16:49Z
2019-06-17T11:16:49Z
2016-02-02
Virus Res. 2016; 213: 116-123
10.1016/j.virusres.2015.11.017
1872-7492
0168-1702
Virus Research
26597719
http://hdl.handle.net/20.500.12105/7781
The 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.
eng
HIV-1
Heterologous expression
Oxidative stress
Phenotypic analysis
Therapeutic target
Vpr
Influence of glutathione availability on cell damage induced by human immunodeficiency virus type 1 viral protein R
research article
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InfluenceGlutathioneAvailabilityCell_2016.pdf
URL
https://repisalud.isciii.es/bitstreams/e9facaa0-083f-40e2-8a3c-2995c21dde4d/download
File
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InfluenceGlutathioneAvailabilityCell_2016.pdf.txt