HLA-DMB restricts human T-cell leukemia virus type-1 (HTLV-1) protein expression via regulation of ATG7 acetylation.
HLA-DMB restricts human T-cell leukemia virus type-1 (HTLV-1) protein expression via regulation of ATG7 acetylation.
复制标题
HLA-DMB 通过调节 ATG7 乙酰化来限制人类 T 细胞白血病病毒 1 型 (HTLV-1) 蛋白的表达。
DOI：
10.1038/s41598-017-14882-z
复制
发表时间：
2017-10-31
影响因子：
4.6
通讯作者：
Yang B
中科院分区：
文献类型：
--
作者：
Wang J;Song D;Liu Y;Lu G;Yang S;Liu L;Gao Z;Ma L;Guo Z;Zhang C;Wang H;Yang B
自噬在病毒感染中的作用是复杂的。虽然自噬已被证明通过消除细胞内病毒和调节适应性免疫在宿主抗病毒防御中起作用，但一些病毒已经进化出分子机制来从中获益。据报道，delta逆转录病毒人t细胞白血病病毒1型（HTLV-1）通过增强自噬体积累来促进其复制。在这里，我们报道了非经典MHC-II蛋白HLA-DM的β链HLA-DMB（一般简称DMB）在HTLV-1转化的t细胞系中有很强的表达，并且可以通过HTLV-1感染诱导Hela， pma分化的THP1 （PMA-THP1）或原代人单核细胞。免疫印迹和实时PCR检测显示，过表达DMB可降低HTLV-1蛋白的表达，而敲低DMB可提高HTLV-1蛋白的表达。免疫印迹和共聚焦显微镜实验表明，过表达DMB可减少HTLV-1诱导的自噬体积累，而敲低DMB则产生相反的效果。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，增加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，我们的发现提示了宿主细胞防御HTLV-1感染的新机制。
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.
登录
查看更多内容
影响因子：
64.8
作者：
Ichimura, Y;Kirisako, T;Ohsumi, Y
通讯作者：
Ohsumi, Y
DOI：
10.1073/pnas.77.12.7415
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
POIESZ, BJ;RUSCETTI, FW;GALLO, RC
通讯作者：
GALLO, RC
影响因子：
19
作者：
Feng, Yuchen;Yao, Zhiyuan;Klionsky, Daniel J.
通讯作者：
Klionsky, Daniel J.
影响因子：
7
作者：
Mellins ED;Stern LJ
通讯作者：
Stern LJ
DOI：
10.1073/pnas.1311669110
发表时间：
2013-11-26
影响因子：
11.1
作者：
Jakobsen, Martin R.;Bak, Rasmus O.;Paludan, Soren R.
通讯作者：
Paludan, Soren R.