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

• Published in: PloS one 2018-11, Vol.13 (11), p.e0207664
• Main Authors: Valadão, Ana Luiza Chaves, Pezzuto, Paula, Silva, Viviane A Oliveira, Gonçalves, Barbara Simonson, Rossi, Átila Duque, da Cunha, Rodrigo Delvecchio, Siani, Antonio Carlos, Tostes, João Batista de Freitas, Trovó, Marcelo, Damasco, Paulo, Gonçalves, Gabriel, Reis, Rui Manuel, Aguiar, Renato Santana, Bento, Cleonice Alves de Melo, Tanuri, Amilcar
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Activation; AIDS; Animal models; Biology and Life Sciences; Care and treatment; CD4 antigen; Cell cycle; Clinical trials; Cytokines; Drug therapy; Epigenetics; Esters; Euphorbia; Euphorbiaceae; HIV; HIV infection; Human immunodeficiency virus; Infections; Inflammation; Isoforms; Kinases; Laboratories; Latency; Latex; Lymphocytes; Lymphocytes T; Materia medica, Vegetable; Medical research; Medicine and Health Sciences; NF-κB protein; Nuclear transport; Peripheral blood mononuclear cells; Phorbol esters; Physical Sciences; Plant extracts; Protein kinase C; Proteins; Risk factors; Transcription; Translocation; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0207664

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.