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迈向人类免疫缺陷病毒消除的途径。

Pathways towards human immunodeficiency virus elimination.

机构信息

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.

Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198-5880, USA.

出版信息

EBioMedicine. 2020 Mar;53:102667. doi: 10.1016/j.ebiom.2020.102667. Epub 2020 Feb 27.

Abstract

Antiretroviral therapy (ART) suppresses human immunodeficiency virus (HIV) infection. Research seeking to transform viral suppression into elimination has generated novel immune, chemical and molecular antiviral agents. However, none, to date, have excised latent integrated proviral DNA or removed infected cells from infected persons. These efforts included, but are not limited to, broadly neutralizing antibodies, "shock" and "kill" latency-reversing agents, innate immune regulators, and sequential long-acting antiretroviral nanoformulated prodrugs and CRISPR-Cas9 gene editing. While, the latter, enabled the complete excision of latent HIV-1 from the host genome success was so far limited. We contend that improvements in antiretroviral delivery, potency, agent specificity, or combinatorial therapies can provide a pathway towards complete HIV elimination.

摘要

抗逆转录病毒疗法(ART)抑制人类免疫缺陷病毒(HIV)感染。旨在将病毒抑制转化为消除的研究产生了新型免疫、化学和分子抗病毒药物。然而,迄今为止,没有一种药物能够切除潜伏的整合前病毒 DNA 或从感染者中清除感染细胞。这些努力包括但不限于广泛中和抗体、“休克”和“杀伤”潜伏逆转剂、先天免疫调节剂,以及顺序长效抗逆转录病毒纳米制剂前药和 CRISPR-Cas9 基因编辑。虽然后者能够成功地从宿主基因组中完全切除潜伏的 HIV-1,但迄今为止,成功的例子仍然有限。我们认为,抗逆转录病毒药物传递、效力、药物特异性或联合治疗的改进可以为彻底消除 HIV 提供一条途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a10/7047153/83c5bbd1d210/gr1.jpg

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