@article {Valad{\~a}o293662, author = {Ana Luiza Chaves Valad{\~a}o and Paula Pezzuto and Viviane A. Oliveira Silva and Barbara Simonson Gon{\c c}alves and {\'A}tila Duque Rossi and Rodrigo Delvecchio da Cunha and Antonio Carlos Siani and Jo{\~a}o Batista de Freitas Tostes and Marcelo Trov{\'o} and Paulo Damasco and Gabriel Gon{\c c}alves and Rui Manuel Reis and Renato Santana de Aguiar and Alves de Melo Cleonice Bento and Amilcar Tanuri}, title = {Reactivation of latent HIV-1 in vitro using an alcoholic extract from Euphorbia umbellata (Euphorbiaceae) latex}, elocation-id = {293662}, year = {2018}, doi = {10.1101/293662}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Euphorbia umbellata (E. umbellata) belongs to Euphorbiaceae family, popularly known as Janauba, and contains in its latex 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 able to increase HIV transcription and reactivate HIV from latency models. This activity was mediated by NF-kB activation followed by nuclear translocation and binding to HIV LTR promoter. In addition, E. umbellate latex extract induced the production of pro inflammatory cytokines together with IL21 in in vitro human PBMC cultures. Our latex extract activates latent HIV in human PBMCs isolated from HIV positive patients as well as latent SIV in non-human primate primary CD4+ T lymphocytes. These results strongly indicate that the phorbol esters present in E. umbellata latex are promising candidate compounds for future clinical trials for shock and kill therapy to promote HIV cure and eradication.}, URL = {https://www.biorxiv.org/content/early/2018/05/03/293662}, eprint = {https://www.biorxiv.org/content/early/2018/05/03/293662.full.pdf}, journal = {bioRxiv} }