Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York.
Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio.
J Med Virol. 2019 Aug;91(8):1571-1576. doi: 10.1002/jmv.25487. Epub 2019 May 1.
A cure for human immunodeficiency virus type-1 (HIV-1) has been hampered by the limitation of current combination antiretroviral therapy (cART) to address the latent reservoirs in HIV-1 patients. One strategy proposed to eradicate these reservoirs is the "shock and kill" approach, where latency-reversing agents (LRAs) are used to reactivate and promote viral cell death and/or immune killing of reactivated cells. Here, we report that curaxin CBL0137, an antitumor compound, can potentiate tumor necrosis factor-α-mediated reactivation of latently infected HIV-1cell lines. Additionally, the single use of CBL0137 is sufficient to reactivate HIV-1 latent reservoirs in peripheral mononuclear cells (PBMCs) isolated from HIV-1 positive, cART-treated, aviremic patients. Thus, CBL0137 possesses capabilities as a LRA and could be considered for the "shock and kill" approach.
人类免疫缺陷病毒 1 型（HIV-1）的治愈方法受到当前联合抗逆转录病毒疗法（cART）的限制，无法解决 HIV-1 患者中的潜伏储库问题。一种旨在消除这些储库的策略是“冲击和杀伤”方法，其中使用潜伏逆转剂（LRA）来重新激活并促进病毒细胞死亡和/或免疫杀伤被重新激活的细胞。在这里，我们报告称，抗肿瘤化合物 curaxin CBL0137 可以增强肿瘤坏死因子-α介导的潜伏感染 HIV-1 细胞系的重新激活。此外，单独使用 CBL0137 就足以重新激活从 HIV-1 阳性、接受 cART 治疗、无病毒血症的患者中分离出的外周单核细胞（PBMC）中的 HIV-1 潜伏储库。因此，CBL0137 具有 LRA 的能力，可以考虑用于“冲击和杀伤”方法。
