Laboratório de Virologia Molecular, Departamento de Genética, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Barretos, Brazil.
PLoS One. 2018 Nov 27;13(11):e0207664. doi: 10.1371/journal.pone.0207664. eCollection 2018.
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.
麻疯树(Euphorbia umbellata)属于大戟科,俗称 Janauba,其乳胶中含有具有生物活性的佛波醇酯组合,可与不同的细胞蛋白激酶 C(PKC)同工型结合。在这里,我们鉴定出存在于麻疯树乳胶醇提物中的脱氧佛波醇酯,它能够增加 HIV 转录并使潜伏状态的病毒重新激活。这种活性可能是通过 NF-κB 激活介导的,随后是核转位并与 HIV LTR 启动子结合。此外,麻疯树乳胶提取物在体外人 PBMC 培养物中诱导产生促炎细胞因子。该乳胶提取物还可激活从 HIV 阳性患者中分离的人 PBMC 中的潜伏病毒,以及非人类灵长类动物原代 CD4+T 淋巴细胞中的潜伏 SIV。总之,这些结果表明,麻疯树乳胶中的佛波醇酯是未来用于休克和杀伤疗法的临床试验的有前途的候选化合物,以促进 HIV 的治愈和根除。