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

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. um...

Descripción completa

Detalles Bibliográficos
Autores: Ana Luiza Chaves Valadão, Paulo Damasco, Gabriel Gonçalves, Rui Manuel Reis, Renato Santana de Aguiar, Cleonice Alves de Melo Bento, Amilcar Tanuri, 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:Brasil
Institución:Universidade Federal de Minas Gerais (UFMG)
Repositorio:Repositório Institucional da UFMG
Idioma:portugués
OAI Identifier:oai:repositorio.ufmg.br:1843/56423
Acceso en línea:https://doi.org/10.1371/journal.pone.0207664
http://hdl.handle.net/1843/56423
http://orcid.org/0000-0002-9639-7940
https://orcid.org/0000-0001-5180-3717
https://orcid.org/0000-0001-9570-8244
https://orcid.org/0000-0001-5919-5242
https://orcid.org/0000-0002-9378-0418
https://orcid.org/0000-0001-6235-8807
https://orcid.org/0000-0002-2951-3964
https://orcid.org/0000-0001-8108-2500
https://orcid.org/0000-0002-0478-2332
Access Level:acceso abierto
Palabra clave:Euphorbia umbellata
HIV infection
Latex extract
Euforbiacea
Infecções por HIV
Latex
Descripción
Sumario: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.