Open AccessReactivation of latent HIV-1 in vitro using an ethanolic extract from Euphorbia umbellata (Euphorbiaceae) latex
Author(s) -
Ana Luiza Chaves Valadão,
Paula Pezzuto,
Viviane Aline Oliveira Silva,
Barbara Simonson Gonçalves,
Átila Duque Rossi,
Rodrigo Delvecchio da Cunha,
Antonio C. Siani,
João Batista de Freitas Tostes,
Marcelo Trovó,
Paulo Vieira Damasco,
G. dos Santos Goncalves,
Rui Manuel Reis,
Renato Santana Aguiar,
Cleonice Alves de Melo Bento,
Amílcar Tanuri
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0207664
Subject(s) - euphorbiaceae , in vitro , euphorbia , peripheral blood mononuclear cell , biology , protein kinase c , traditional medicine , pharmacology , phorbol , biochemistry , kinase , medicine , botany
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.