复杂的反转录病毒-人T细胞白血病病毒1型（HTLV-1）主要在体内感染CD4+ T细胞。细胞内感染的传播需要病毒感染细胞与靶细胞直接接触。最近研究表明，HTLV-1附属蛋白HBZ通过激活细胞内黏附分子1（ICAM-1）表达增强HTLV-1感染，从而促进感染细胞与靶细胞的结合和病毒学突触的形成。在这个研究中，我们展示了HBZ通过激活肌肥大蛋白（MyoF）的表达进一步增强了HTLV-1的感染，该蛋白在膜融合和修复以及小泡运输中发挥作用。来自ChIP分析和定量逆转录酶PCR的结果表明，HBZ在MYOF基因的两个增强剂位点与c-Jun或JunB形成复合物，并通过招募共激活剂p300/CBP激活转录。在HTLV-1感染的T细胞中，使用药物WJ460特异性抑制MyoF或使用shRNA介导的MyoF沉默能够降低感染效率。这种效应与细胞粘附的减少和HTLV-1包膜（Env）表面单元（SU）和跨膜区域（TM）的细胞内丰度减少有关。溶酶体蛋白酶抑制剂部分恢复了WJ460处理的细胞中的SU水平，并且MyoF沉默增加了SU定位到LAMP-2位点，表明MyoF限制了SU运输到溶酶体进行降解。与这些效应一致的是，与无细胞病毒颗粒相关的SU更少。这些数据表明，MyoF通过调节Env运输和细胞粘附有助于HTLV-1感染。 版权：©2023 Polakowski等人。这是一篇开放获取文章，根据创作公共许可证无限制使用，分发和再现任何媒介，只要原作者和来源得到贷记。

The complex retrovirus, human T-cell leukemia virus type 1 (HTLV-1), primarily infects CD4+ T-cells in vivo. Infectious spread within this cell population requires direct contact between virally-infected and target cells. The HTLV-1 accessory protein, HBZ, was recently shown to enhance HTLV-1 infection by activating intracellular adhesion molecule 1 (ICAM-1) expression, which promotes binding of infected cells to target cells and facilitates formation of a virological synapse. In this study we show that HBZ additionally enhances HTLV-1 infection by activating expression of myoferlin (MyoF), which functions in membrane fusion and repair and vesicle transport. Results from ChIP assays and quantitative reverse transcriptase PCR indicate that HBZ forms a complex with c-Jun or JunB at two enhancer sites within the MYOF gene and activates transcription through recruitment of the coactivator p300/CBP. In HTLV-1-infected T-cells, specific inhibition of MyoF using the drug, WJ460, or shRNA-mediated knockdown of MyoF reduced infection efficiency. This effect was associated with a decrease in cell adhesion and an intracellular reduction in the abundance of HTLV-1 envelope (Env) surface unit (SU) and transmembrane domain (TM). Lysosomal protease inhibitors partially restored SU levels in WJ460-treated cells, and SU localization to LAMP-2 sites was increased by MyoF knockdown, suggesting that MyoF restricts SU trafficking to lysosomes for degradation. Consistent with these effects, less SU was associated with cell-free virus particles. Together, these data suggest that MyoF contributes to HTLV-1 infection through modulation of Env trafficking and cell adhesion.Copyright: © 2023 Polakowski et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.