Myeloid neddylation targets IRF7 and promotes host innate immunity against RNA viruses.
Neddylation, an important type of post-translational modification, has been implicated in innate and adapted immunity. But the role of neddylation in innate immune response against RNA viruses remains elusive. Here we report that neddylation promotes RNA virus-induced type I IFN production, especial...
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2021
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oai:doaj.org-article:6c71f2746fe440d784de08ef8d7813272021-12-02T20:00:12ZMyeloid neddylation targets IRF7 and promotes host innate immunity against RNA viruses.1553-73661553-737410.1371/journal.ppat.1009901https://doaj.org/article/6c71f2746fe440d784de08ef8d7813272021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009901https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Neddylation, an important type of post-translational modification, has been implicated in innate and adapted immunity. But the role of neddylation in innate immune response against RNA viruses remains elusive. Here we report that neddylation promotes RNA virus-induced type I IFN production, especially IFN-α. More importantly, myeloid deficiency of UBA3 or NEDD8 renders mice less resistant to RNA virus infection. Neddylation is essential for RNA virus-triggered activation of Ifna gene promoters. Further exploration has revealed that mammalian IRF7undergoes neddylation, which is enhanced after RNA virus infection. Even though neddylation blockade does not hinder RNA virus-triggered IRF7 expression, IRF7 mutant defective in neddylation exhibits reduced ability to activate Ifna gene promoters. Neddylation blockade impedes RNA virus-induced IRF7 nuclear translocation without hindering its phosphorylation and dimerization with IRF3. By contrast, IRF7 mutant defective in neddylation shows enhanced dimerization with IRF5, an Ifna repressor when interacting with IRF7. In conclusion, our data demonstrate that myeloid neddylation contributes to host anti-viral innate immunity through targeting IRF7 and promoting its transcriptional activity.Min ZhaoYaolin ZhangXiqin YangJiayang JinZhuo ShenXiaoyao FengTao ZouLijiao DengDaohai ChengXueting ZhangCheng QinChunxiao NiuZhenjie YeXueying ZhangJia HeChunmei HouGe LiGencheng HanQianqian ChengQingyang WangLin WeiJie DongJiyan ZhangPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 9, p e1009901 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Min Zhao Yaolin Zhang Xiqin Yang Jiayang Jin Zhuo Shen Xiaoyao Feng Tao Zou Lijiao Deng Daohai Cheng Xueting Zhang Cheng Qin Chunxiao Niu Zhenjie Ye Xueying Zhang Jia He Chunmei Hou Ge Li Gencheng Han Qianqian Cheng Qingyang Wang Lin Wei Jie Dong Jiyan Zhang Myeloid neddylation targets IRF7 and promotes host innate immunity against RNA viruses. |
| description |
Neddylation, an important type of post-translational modification, has been implicated in innate and adapted immunity. But the role of neddylation in innate immune response against RNA viruses remains elusive. Here we report that neddylation promotes RNA virus-induced type I IFN production, especially IFN-α. More importantly, myeloid deficiency of UBA3 or NEDD8 renders mice less resistant to RNA virus infection. Neddylation is essential for RNA virus-triggered activation of Ifna gene promoters. Further exploration has revealed that mammalian IRF7undergoes neddylation, which is enhanced after RNA virus infection. Even though neddylation blockade does not hinder RNA virus-triggered IRF7 expression, IRF7 mutant defective in neddylation exhibits reduced ability to activate Ifna gene promoters. Neddylation blockade impedes RNA virus-induced IRF7 nuclear translocation without hindering its phosphorylation and dimerization with IRF3. By contrast, IRF7 mutant defective in neddylation shows enhanced dimerization with IRF5, an Ifna repressor when interacting with IRF7. In conclusion, our data demonstrate that myeloid neddylation contributes to host anti-viral innate immunity through targeting IRF7 and promoting its transcriptional activity. |
| format |
article |
| author |
Min Zhao Yaolin Zhang Xiqin Yang Jiayang Jin Zhuo Shen Xiaoyao Feng Tao Zou Lijiao Deng Daohai Cheng Xueting Zhang Cheng Qin Chunxiao Niu Zhenjie Ye Xueying Zhang Jia He Chunmei Hou Ge Li Gencheng Han Qianqian Cheng Qingyang Wang Lin Wei Jie Dong Jiyan Zhang |
| author_facet |
Min Zhao Yaolin Zhang Xiqin Yang Jiayang Jin Zhuo Shen Xiaoyao Feng Tao Zou Lijiao Deng Daohai Cheng Xueting Zhang Cheng Qin Chunxiao Niu Zhenjie Ye Xueying Zhang Jia He Chunmei Hou Ge Li Gencheng Han Qianqian Cheng Qingyang Wang Lin Wei Jie Dong Jiyan Zhang |
| author_sort |
Min Zhao |
| title |
Myeloid neddylation targets IRF7 and promotes host innate immunity against RNA viruses. |
| title_short |
Myeloid neddylation targets IRF7 and promotes host innate immunity against RNA viruses. |
| title_full |
Myeloid neddylation targets IRF7 and promotes host innate immunity against RNA viruses. |
| title_fullStr |
Myeloid neddylation targets IRF7 and promotes host innate immunity against RNA viruses. |
| title_full_unstemmed |
Myeloid neddylation targets IRF7 and promotes host innate immunity against RNA viruses. |
| title_sort |
myeloid neddylation targets irf7 and promotes host innate immunity against rna viruses. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/6c71f2746fe440d784de08ef8d781327 |
| work_keys_str_mv |
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| _version_ |
1718375727737339904 |