An amphipathic peptide targeting the gp41 cytoplasmic tail kills HIV-1 virions and infected cells
An amphipathic peptide targeting the gp41 cytoplasmic tail kills HIV-1 virions and infected cells
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靶向 gp41 胞质尾部的两亲肽可杀死 HIV-1 病毒粒子和受感染细胞
DOI：
10.1126/scitranslmed.aaz2254
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发表时间：
2020-06-03
影响因子：
17.1
通讯作者：
Lu，Lu
中科院分区：
文献类型：
--
作者：
Wang，Qian;Su，Shan;Lu，Lu
来自HIV包膜蛋白的肽在体外灭活HIV-1病毒粒子并抑制慢性shiv感染猕猴的病毒载量。对现有抗病毒药物的耐药性促使人们需要找到针对艾滋病毒的新方法。Wang等人从HIV包膜蛋白中筛选了一个肽库，以找到能够抑制病毒的肽库。其中一种肽F9170靶向HIV gp41，对游离病毒粒子或HIV感染细胞有效。这种肽在小鼠中似乎没有毒性或免疫原性，并且足够小，可以穿透含有HIV病毒库的组织。用短期疗程的F9170治疗的猿猴hiv感染猕猴的病毒载量大幅下降。虽然还需要进一步的测试和开发，但有一天它可能会成为艾滋病毒新治疗方案的一部分。由于抗逆转录病毒联合治疗，艾滋病毒相关的发病率和死亡率显著下降，但艾滋病毒很容易发生突变，产生耐药性。开发针对以前未定义靶点的抗病毒药物对于治疗现有的耐药HIV毒株至关重要。一些来自HIV-1包膜糖蛋白（Env, gp120-gp41）的肽已被证明能有效抑制HIV-1感染。因此，我们从HIV-1 Env中筛选了一个肽库，并从细胞质区发现了一个肽，命名为F9170，它能够有效地灭活HIV-1病毒粒子，诱导HIV-1感染细胞坏死，并重新激活潜伏感染的细胞。F9170特异性靶向HIV-1 Env保守的细胞质尾部，有效破坏病毒膜的完整性。短期单给药F9170可将慢性shiv感染猕猴体内的病毒载量控制在检测极限以下。F9170可以进入大脑和淋巴结，这是HIV潜伏的解剖储存库。因此，F9170有望成为治疗HIV的候选药物。
A peptide from the HIV envelope protein inactivates HIV-1 virions in vitro and suppresses the viral load of chronically SHIV-infected macaques. Making HIV its own worst enemy Resistance to existing antivirals drives the need for identifying new ways to target HIV. Wang et al. screened a library of peptides from the HIV envelope protein to find ones that could inhibit the virus. One peptide, F9170, targeted HIV gp41 and was effective against free virions or HIV-infected cells. This peptide did not seem to be toxic or immunogenic in mice and is small enough to penetrate tissues that harbor HIV reservoirs. Simian-HIV–infected macaques treated with a short course of F9170 experienced a substantial drop in viral loads. Although further testing and development are needed, it could one day be part of a new treatment regimen for HIV. HIV-associated morbidity and mortality have markedly declined because of combinational antiretroviral therapy, but HIV readily mutates to develop drug resistance. Developing antivirals against previously undefined targets is essential to treat existing drug-resistant HIV strains. Some peptides derived from HIV-1 envelope glycoprotein (Env, gp120-gp41) have been shown to be effective in inhibiting HIV-1 infection. Therefore, we screened a peptide library from HIV-1 Env and identified a peptide from the cytoplasmic region, designated F9170, able to effectively inactivate HIV-1 virions and induce necrosis of HIV-1–infected cells, and reactivated latently infected cells. F9170 specifically targeted the conserved cytoplasmic tail of HIV-1 Env and effectively disrupted the integrity of the viral membrane. Short-term monoadministration of F9170 controlled viral loads to below the limit of detection in chronically SHIV-infected macaques. F9170 can enter the brain and lymph nodes, anatomic reservoirs for HIV latency. Therefore, F9170 shows promise as a drug candidate for HIV treatment.