Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Exotic Disease Group, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), Tokyo 187-0022, Japan.
Viruses. 2022 Mar 31;14(4):740. doi: 10.3390/v14040740.
Human T-cell leukemia virus type 1 (HTLV-1) causes serious and intractable diseases in some carriers after infection. The elimination of infected cells is considered important to prevent this onset, but there are currently no means by which to accomplish this. We previously developed "virotherapy", a therapeutic method that targets and kills HTLV-1-infected cells using a cytolytic recombinant vesicular stomatitis virus (rVSV). Infection with rVSV expressing an HTLV-1 primary receptor elicits therapeutic effects on HTLV-1-infected envelope protein (Env)-expressing cells in vitro and in vivo. Simian T-cell leukemia virus type 1 (STLV-1) is closely related genetically to HTLV-1, and STLV-1-infected Japanese macaques (JMs) are considered a useful HTLV-1 surrogate, non-human primate model in vivo. Here, we performed an in vitro drug evaluation of rVSVs against STLV-1 as a preclinical study. We generated novel rVSVs encoding the STLV-1 primary receptor, simian glucose transporter 1 (JM GLUT1), with or without an AcGFP reporter gene. Our data demonstrate that these rVSVs specifically and efficiently infected/eliminated the STLV-1 Env-expressing cells in vitro. These results indicate that rVSVs carrying the STLV-1 receptor could be an excellent candidate for unique anti-STLV-1 virotherapy; therefore, such antivirals can now be applied to STLV-1-infected JMs to determine their therapeutic usefulness in vivo.
人类 T 细胞白血病病毒 1 型（HTLV-1）在感染后会使一些携带者患上严重且难以治愈的疾病。消除受感染的细胞被认为对于预防这种发病至关重要，但目前尚无实现这一目标的方法。我们之前开发了“病毒疗法”，这是一种使用细胞溶解重组单纯疱疹病毒（rVSV）靶向和杀死 HTLV-1 感染细胞的治疗方法。感染表达 HTLV-1 主要受体的 rVSV 在体外和体内对 HTLV-1 感染包膜蛋白（Env）表达细胞产生治疗作用。猿猴 T 细胞白血病病毒 1 型（STLV-1）在遗传上与 HTLV-1 密切相关，感染 STLV-1 的日本猕猴（JM）被认为是一种有用的 HTLV-1 替代物，是体内非人类灵长类动物模型。在这里，我们进行了针对 STLV-1 的 rVSV 体外药物评价，作为临床前研究。我们生成了新型 rVSV，编码 STLV-1 主要受体，即猿猴葡萄糖转运蛋白 1（JM GLUT1），带有或不带有 AcGFP 报告基因。我们的数据表明，这些 rVSV 能够在体外特异性和有效地感染/消除 STLV-1 Env 表达细胞。这些结果表明，携带 STLV-1 受体的 rVSV 可能是一种优秀的抗 STLV-1 病毒疗法的候选物；因此，现在可以将这些抗病毒药物应用于感染 STLV-1 的 JM 中，以确定它们在体内的治疗效果。
