Development of a Monoclonal Antibody Targeting HTLV-1 Envelope gp46 Glycoprotein and Its Application to Near-Infrared Photoimmuno-Antimicrobial Strategy.

Development of a Monoclonal Antibody Targeting HTLV-1 Envelope gp46 Glycoprotein and Its Application to Near-Infrared Photoimmuno-Antimicrobial Strategy.
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DOI:
10.3390/v14102153
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发表时间:
2022-09-29
期刊:
Viruses
影响因子:
--
通讯作者:
Ryo A
Ryo A
中科院分区:
其他
文献类型:
--
作者:
Hatayama Y;Yamaoka Y;Morita T;Jeremiah SS;Miyakawa K;Nishi M;Kimura Y;Mitsunaga M;Iwase T;Kimura H;Yamamoto N;Takaori-Kondo A;Hasegawa H;Ryo A

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人类 T 细胞白血病病毒 1 型 (HTLV-1) 是一种逆转录病毒,可引起成人 T 细胞白血病淋巴瘤、HTLV-1 相关脊髓病/热带痉挛性截瘫和 HTLV-1 葡萄膜炎。目前,尚无针对 HTLV-1 感染的抗逆转录病毒疗法或疫苗。本研究旨在开发一种针对 HTLV-1 包膜蛋白 (Env) 的抗体,并将其应用于近红外光免疫抗菌策略 (NIR-PIAS),以消除 HTLV-1 感染的细胞。我们通过脂质体和重组蛋白的复合物进行免疫,建立了针对 HTLV-1 Env 的小鼠单克隆抗体 (mAb)。详细的表位作图表明,其中一种单克隆抗体与 gp46 富含脯氨酸的区域结合,并且没有表现出明显的抑制病毒感染的中和活性。相反,mAb 很少内化到细胞内,并保留在 HTLV-1 感染细胞的细胞表面上。与光敏染料 IRDye700Dx 结合的抗体可识别 HTLV-1 感染的细胞,并在近红外辐射后杀死它们。这些结果表明,新型 mAb 和 NIR-PIAS 可以开发为针对 HTLV-1 感染细胞的新靶向治疗工具。
Human T-cell leukemia virus type 1 (HTLV-1), a retrovirus, causes adult T-cell leukemia-lymphoma, HTLV-1 associated myelopathy/tropical spastic paraparesis, and HTLV-1 uveitis. Currently, no antiretroviral therapies or vaccines are available for HTLV-1 infection. This study aimed to develop an antibody against the HTLV-1 envelope protein (Env) and apply it to a near-infrared photoimmuno-antimicrobial strategy (NIR-PIAS) to eliminate HTLV-1 infected cells. We established mouse monoclonal antibodies (mAbs) against HTLV-1 Env by immunization with a complex of liposome and the recombinant protein. Detailed epitope mapping revealed that one of the mAbs bound to the proline-rich region of gp46 and exhibited no obvious neutralizing activity to inhibit viral infection. Instead, the mAb was rarely internalized intracellularly and remained on the cell surface of HTLV-1-infected cells. The antibody conjugated to the photosensitive dye IRDye700Dx recognized HTLV-1 infected cells and killed them following NIR irradiation. These results suggest that the novel mAb and NIR-PIAS could be developed as a new targeted therapeutic tool against HTLV-1 infected cells.
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无症状 HTLV-1 携带者的人类 T 细胞白血病病毒 I 型(HTLV-1)前病毒载量和疾病进展:日本的一项全国性前瞻性研究
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