Li Chunfeng, Deng Yong-Qiang, Wang Shuo, Ma Feng, Aliyari Roghiyh, Huang Xing-Yao, Zhang Na-Na, Watanabe Momoko, Dong Hao-Long, Liu Ping, Li Xiao-Feng, Ye Qing, Tian Min, Hong Shuai, Fan Junwan, Zhao Hui, Li Lili, Vishlaghi Neda, Buth Jessie E, Au Connie, Liu Ying, Lu Ning, Du Peishuang, Qin F Xiao-Feng, Zhang Bo, Gong Danyang, Dai Xinghong, Sun Ren, Novitch Bennett G, Xu Zhiheng, Qin Cheng-Feng, Cheng Genhong
Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, 100005 Beijing, China; Suzhou Institute of Systems Medicine, Suzhou, 215123 Jiangsu, China; Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 100071 Beijing, China.
Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 100071 Beijing, China.
Immunity. 2017 Mar 21;46(3):446-456. doi: 10.1016/j.immuni.2017.02.012. Epub 2017 Mar 14.
Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques. 25HC suppressed ZIKV infection and reduced tissue damage in human cortical organoids and the embryonic brain of the ZIKV-induced mouse microcephaly model. Our findings highlight the protective role of CH25H during ZIKV infection and the potential use of 25HC as a natural antiviral agent to combat ZIKV infection and prevent ZIKV-associated outcomes, such as microcephaly.
寨卡病毒（ZIKV）因其全球传播以及与严重先天性疾病的关联，已成为一种公共卫生威胁。宿主对寨卡病毒感染的免疫反应尚未完全阐明，目前也没有有效的治疗方法。在此，我们证明胆固醇-25-羟化酶（CH25H）在寨卡病毒感染时被诱导产生，其酶促产物25-羟胆固醇（25HC）是宿主抵御寨卡病毒的关键介质。添加合成的25HC可通过阻断病毒进入在体外抑制寨卡病毒感染，用25HC治疗可降低小鼠和恒河猴的病毒血症并提供对寨卡病毒的保护。25HC在人皮质类器官和寨卡病毒诱导的小鼠小头畸形模型的胚胎脑中抑制了寨卡病毒感染并减少了组织损伤。我们的研究结果突出了CH25H在寨卡病毒感染期间的保护作用，以及25HC作为一种天然抗病毒剂对抗寨卡病毒感染和预防寨卡病毒相关后果（如小头畸形）的潜在用途。
