Reactivation of latent HIV-1 in vitro using an ethanolic extract from Euphorbia umbellata (Euphorbiaceae) latex

Ana Luiza Chaves Valadão, Paula Pezzuto, Viviane A. Oliveira Silva, Barbara Simonson Gonçalves, Átila Duque Rossi, Rodrigo Delvecchio da Cunha, Antonio Carlos Siani, João Batista de Freitas Tostes, Marcelo Trovó, Paulo Damasco, Gabriel Gonçalves, Rui Manuel Reis (+4 others)
2018 PLoS ONE  
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 deoxiphorbol 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
more » ... 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.
doi:10.1371/journal.pone.0207664 fatcat:6dvossh7ezcopgjtdeoovx2cue