Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan Province, China.
Henan Key Laboratory of immunology and targeted drugs, Xinxiang Medical University, Xinxiang, 453003, Henan Province, China.
Sci Rep. 2017 Oct 31;7(1):14416. doi: 10.1038/s41598-017-14882-z.
The roles of autophagy in viral infection are complicated. While autophagy has been shown to function in host antiviral defense by eliminating intracellular viruses and regulating adaptive immunity, several viruses have evolved molecular mechanisms to get benefits from it. The deltaretrovirus human T-cell leukemia virus type-1 (HTLV-1) has been reported to profit its replication from enhancing autophagosome accumulation. Here, we reported that HLA-DMB (generally referred to here as DMB), the beta chain of the non-classical MHC-II protein HLA-DM, had strong expression in HTLV-1-transformed T-cell lines and could be induced in Hela, PMA-differentiated THP1 (PMA-THP1) or primary human monocytes by HTLV-1 infection. Immunoblot and real-time PCR assays demonstrated that overexpression of DMB decreased HTLV-1 protein expression while the knockdown of DMB increased HTLV-1 protein expression. Immunoblot and confocal microscopy assays indicated that overexpression of DMB decreased HTLV-1 induced autophagosome accumulation while the knockdown of DMB yielded the opposite effects. Coimmunoprecipitation and immunoprecipitation experiments suggested DMB interacted with autophagy-related gene (ATG) 7 and increased the acetylation of ATG7. Taken together, these results suggested DMB modulated HTLV-1 protein expression through regulation of autophagosome accumulation and our findings suggested a new mechanism by which the host cells defended against HTLV-1 infection.
自噬在病毒感染中的作用较为复杂。自噬可通过清除细胞内病毒和调节适应性免疫来发挥宿主抗病毒防御作用，但几种病毒已进化出分子机制从中获益。δ逆转录病毒人类 T 细胞白血病病毒 1 型（HTLV-1）已被报道通过增强自噬体积累来促进其复制。在这里，我们报道了 HLA-DMB（通常称为 DMB），即 HLA-DM 非经典 MHC-II 蛋白的β链，在 HTLV-1 转化的 T 细胞系中表达强烈，并可被 HTLV-1 感染诱导在 Hela、PMA 分化的 THP1（PMA-THP1）或原代人单核细胞中表达。免疫印迹和实时 PCR 检测表明，DMB 的过表达降低了 HTLV-1 蛋白的表达，而 DMB 的敲低则增加了 HTLV-1 蛋白的表达。免疫印迹和共聚焦显微镜检测表明，DMB 的过表达降低了 HTLV-1 诱导的自噬体积累，而 DMB 的敲低则产生了相反的效果。共免疫沉淀和免疫沉淀实验表明 DMB 与自噬相关基因（ATG）7 相互作用，并增加了 ATG7 的乙酰化。综上所述，这些结果表明 DMB 通过调节自噬体积累来调节 HTLV-1 蛋白的表达，我们的研究结果提示了宿主细胞抵御 HTLV-1 感染的一种新机制。
