估计有1000万人被感染,Deltetro病毒人类T细胞嗜淋巴细胞病毒1型(HTLV-1)是仅次于HIV-1的人类第二大流行致病性逆转录病毒。像HIV-1一样,HTLV-1通过潜伏感染的CD4+T细胞库在宿主中压倒性地持续存在。尽管大多数患者无症状,HTLV-1相关病理通常使人衰弱,包括成人T细胞白血病/淋巴瘤(ATLL),在成年后出现,尽管接受了治疗,但预后差,总生存期短。奇怪的是,ATLL发展的最强指标是通过母乳喂养获得HTLV-1.对于HTLV-1没有治疗或预防方案。然而,抗逆转录病毒药物(ARV),靶向必需的逆转录病毒酶,已经开发并转化了HIV疗法。由于逆转录病毒酶活性位点的结构是高度保守的,一些HIV特异性化合物对HTLV-1具有活性。这里,我们扩大我们的工作,这表明整合酶链转移抑制剂(INSTIs)和一些核苷逆转录酶抑制剂(NRTIs)在细胞培养中阻断HTLV-1的传播。具体来说,我们发现dolutegravir,INSTI目前推荐作为所有新的联合抗逆转录病毒疗法处方的基础,NRTI替诺福韦的最新前药配方,替诺福韦艾拉酚胺,还能有效抑制HTLV-1感染。我们的结果,如果在临床环境中复制,通过在HTLV-1流行地区简单地重新利用已经广泛使用的HIV药丸,可以看到HTLV-1的传播率和ATLL等与HTLV-1相关的病理的未来病例数急剧减少。考虑到我们的发现,用古老的医学说法“预防胜于治疗”,我们强烈建议在即将进行的HTLV-1临床试验中纳入INSTIs和替诺福韦前药作为潜在的预防措施.
With an estimated 10 million people infected, the deltaretrovirus human T-cell lymphotropic virus type 1 (HTLV-1) is the second most prevalent pathogenic retrovirus in humans after HIV-1. Like HIV-1, HTLV-1 overwhelmingly persists in a host via a reservoir of latently infected CD4+ T cells. Although most patients are asymptomatic, HTLV-1-associated pathologies are often debilitating and include adult T-cell leukaemia/lymphoma (ATLL), which presents in mature adulthood and is associated with poor prognosis with short overall survival despite treatment. Curiously, the strongest indicator for the development of ATLL is the acquisition of HTLV-1 through breastfeeding. There are no therapeutic or preventative regimens for HTLV-1. However, antiretrovirals (ARVs), which target the essential retrovirus enzymes, have been developed for and transformed HIV therapy. As the architectures of retroviral enzyme active sites are highly conserved, some HIV-specific compounds are active against HTLV-1. Here, we expand on our work, which showed that integrase strand transfer inhibitors (INSTIs) and some nucleoside reverse transcriptase inhibitors (NRTIs) block HTLV-1 transmission in cell culture. Specifically, we find that dolutegravir, the INSTI currently recommended as the basis of all new combination antiretroviral therapy prescriptions, and the latest prodrug formula of the NRTI tenofovir, tenofovir alafenamide, also potently inhibit HTLV-1 infection. Our results, if replicated in a clinical setting, could see transmission rates of HTLV-1 and future caseloads of HTLV-1-associated pathologies like ATLL dramatically cut via the simple repurposing of already widely available HIV pills in HTLV-1 endemic areas. Considering our findings with the old medical saying \"it is better to prevent than cure\", we highly recommend the inclusion of INSTIs and tenofovir prodrugs in upcoming HTLV-1 clinical trials as potential prophylactics.