Reactivation of latent HIV-1 in vitro using an ethanolic extract from Euphorbia umbellata (Euphorbiaceae) latex.
Ana Luiza Chaves ValadãoPaula PezzutoViviane A Oliveira SilvaBarbara Simonson GonçalvesÁtila Duque RossiRodrigo Delvecchio da CunhaAntonio Carlos SianiJoão Batista de Freitas TostesMarcelo TrovóPaulo DamascoGabriel GonçalvesRui Manuel Vieira ReisRenato Santana AguiarCleonice Alves de Melo BentoAmilcar TanuriPublished in: PloS one (2018)
Euphorbia umbellata (E. umbellata) belongs to Euphorbiaceae family, popularly known as Janauba, and its latex contains a combination of phorbol esters with biological activities described to different cellular protein kinase C (PKC) isoforms. Here, we identified deoxi-phorbol esters present in E. umbellata latex alcoholic extract that are able to increase HIV transcription and reactivate virus from latency models. This activity is probably mediated by NF-kB activation followed by nuclear translocation and binding to the HIV LTR promoter. In addition, E. umbellata latex extract induced the production of pro inflammatory cytokines in vitro in human PBMC cultures. This latex extract also activates latent virus in human PBMCs isolated from HIV positive patients as well as latent SIV in non-human primate primary CD4+ T lymphocytes. Together, these results indicate that the phorbol esters present in E. umbellata latex are promising candidate compounds for future clinical trials for shock and kill therapies to promote HIV cure and eradication.
Keyphrases
- hiv positive
- antiretroviral therapy
- men who have sex with men
- hiv infected
- south africa
- human immunodeficiency virus
- endothelial cells
- hiv testing
- oxidative stress
- hiv aids
- hepatitis c virus
- clinical trial
- anti inflammatory
- pluripotent stem cells
- high glucose
- induced pluripotent stem cells
- end stage renal disease
- protein kinase
- dna methylation
- immune response
- transcription factor
- ejection fraction
- signaling pathway
- gene expression
- diabetic rats
- study protocol
- chronic kidney disease
- inflammatory response
- toll like receptor
- helicobacter pylori
- pi k akt
- nuclear factor
- double blind