|
25-Hydroxycholesterol Protects Host against Zika Virus Infection and Its Associated Microcephaly in a Mouse Model
Chunfeng Li, Yong-Qiang Deng, Shuo Wang, Feng Ma, Roghiyh Aliyari, Xing-Yao Huang, Na-Na Zhang, Momoko Watanabe, Hao-Long Dong, Ping Liu, Xiao-Feng Li, Qing Ye, Min Tian, Shuai Hong, Junwan Fan, Hui Zhao, Lili Li, Neda Vishlaghi, Jessie E. Buth, Connie Au, Ying Liu, Ning Lu, Peishuang Du, F. Xiao-Feng Qin, Bo Zhang, Danyang Gong, Xinghong Dai, Ren Sun, Bennett G. Novitch, Zhiheng Xu, Cheng-Feng Qin, Genhong Cheng
Immunity
Abstract
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 infectionin 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.
|
论文编号: |
DOI:10.1016/j.immuni.2017.02.012 |
论文题目: |
25-Hydroxycholesterol Protects Host against Zika Virus Infection and Its Associated Microcephaly in a Mouse Model |
英文论文题目: |
25-Hydroxycholesterol Protects Host against Zika Virus Infection and Its Associated Microcephaly in a Mouse Model |
第一作者: |
Chunfeng Li, Yong-Qiang Deng, Shuo Wang, Feng Ma, Roghiyh Aliyari, Xing-Yao Huang, Na-Na Zhang, Momoko Watanabe, Hao-Long Dong, Ping Liu, Xiao-Feng Li, Qing Ye, Min Tian, Shuai Hong, Junwan Fan, Hui Zhao, Lili Li, Neda Vishlaghi, Jessie E. Buth, Connie Au, Ying Liu, Ning Lu, Peishuang Du, F. Xiao-Feng Qin, Bo Zhang, Danyang Gong, Xinghong Dai, Ren Sun, Bennett G. Novitch, Zhiheng Xu, Cheng-Feng Qin, Genhong Cheng |
英文第一作者: |
Chunfeng Li, Yong-Qiang Deng, Shuo Wang, Feng Ma, Roghiyh Aliyari, Xing-Yao Huang, Na-Na Zhang, Momoko Watanabe, Hao-Long Dong, Ping Liu, Xiao-Feng Li, Qing Ye, Min Tian, Shuai Hong, Junwan Fan, Hui Zhao, Lili Li, Neda Vishlaghi, Jessie E. Buth, Connie Au, Ying Liu, Ning Lu, Peishuang Du, F. Xiao-Feng Qin, Bo Zhang, Danyang Gong, Xinghong Dai, Ren Sun, Bennett G. Novitch, Zhiheng Xu, Cheng-Feng Qin, Genhong Cheng |
联系作者: |
|
英文联系作者: |
|
外单位作者单位: |
|
英文外单位作者单位: |
|
发表年度: |
2017-09-30 |
卷: |
|
期: |
|
页码: |
|
摘要: |
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 infectionin 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. |
英文摘要: |
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 infectionin 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. |
刊物名称: |
Immunity |
英文刊物名称: |
Immunity |
论文全文: |
|
英文论文全文: |
|
全文链接: |
|
其它备注: |
Chunfeng Li, Yong-Qiang Deng, Shuo Wang, Feng Ma, Roghiyh Aliyari, Xing-Yao Huang, Na-Na Zhang, Momoko Watanabe, Hao-Long Dong, Ping Liu, Xiao-Feng Li, Qing Ye, Min Tian, Shuai Hong, Junwan Fan, Hui Zhao, Lili Li, Neda Vishlaghi, Jessie E. Buth, Connie Au, Ying Liu, Ning Lu, Peishuang Du, F. Xiao-Feng Qin, Bo Zhang, Danyang Gong, Xinghong Dai, Ren Sun, Bennett G. Novitch, Zhiheng Xu, Cheng-Feng Qin, Genhong Cheng. 25-Hydroxycholesterol Protects Host against Zika Virus Infection and Its Associated Microcephaly in a Mouse Model. Immunity. DOI:10.1016/j.immuni.2017.02.012 |
英文其它备注: |
|
学科: |
|
英文学科: |
|
影响因子: |
|
第一作者所在部门: |
|
英文第一作者所在部门: |
|
论文出处: |
|
英文论文出处: |
|
论文类别: |
|
英文论文类别: |
|
参与作者: |
|
英文参与作者: |
|
|