Induction of co-inhibitory molecule CTLA-4 by human papillomavirus E7 protein through downregulation of histone methyltransferase JHDM1B expression
Induction of co-inhibitory molecule CTLA-4 by human papillomavirus E7 protein through downregulation of histone methyltransferase JHDM1B expression
复制标题
人乳头瘤病毒E7蛋白通过下调组蛋白甲基转移酶JHDM1B表达诱导共抑制分子CTLA-4
DOI：
10.1016/j.virol.2019.10.001
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发表时间：
2019-12-01
期刊：
影响因子：
3.7
通讯作者：
Cheng, Hao
中科院分区：
文献类型：
--
作者：
Zhou, Qiang;Chen, Luxia;Cheng, Hao
人乳头瘤病毒引起各种皮肤疾病，甚至癌症。不幸的是，由于HPV能够逃避免疫介导的根除，宿主免疫系统经常不能产生有效的HPV感染反应，尽管HPV抑制宿主抗病毒免疫的详细机制尚不完全清楚。在这项研究中，我们报道了HPV E7癌蛋白在上皮细胞中诱导共抑制分子细胞毒性T淋巴细胞相关抗原-4 （CTLA-4）表达的新作用。在机制上，HPV E7蛋白下调了巨鼠姬C组蛋白去甲基化酶1B （JHDM1B）的细胞丰度，增加了CTLA-4启动子区域内H3K36的甲基化水平。我们的发现扩大了目前对hpv介导的免疫逃避机制的理解，并可能有助于开发最佳的抗hpv治疗策略和相关药物。
Human papillomavirus causes various skin diseases and even cancer. Unfortunately, the host immune system often fails to generate effective responses against HPV infection due to the ability of HPV to evade immune-mediated eradication, although the detailed mechanisms by which HPV inhibits host antiviral immunity are not fully understood. In this study, we reported a novel role of HPV E7 oncoprotein in inducing the expression of co-inhibitory molecule cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) in cells of epithelial origin. Mechanistically, HPV E7 protein downregulated the cellular abundance of Jumonji C histone demethylase 1B (JHDM1B), increasing the levels of H3K36 methylation within the promoter region of CTLA-4. Our findings expand the current understanding of HPV-mediated immune evasion mechanisms and may be helpful in developing optimal anti-HPV therapeutic strategies and relevant drugs.