DHAV-1 Blocks the Signaling Pathway Upstream of Type I Interferon by Inhibiting the Interferon Regulatory Factor 7 Protein
Duck hepatitis A virus (DHAV), which mainly infects 1- to 4-week-old ducklings, has a fatality rate of 95% and poses a huge economic threat to the duck industry. However, the mechanism by which DHAV-1 regulates the immune response of host cells is rarely reported. This study examined whether DHAV-1...
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2021
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oai:doaj.org-article:9217336816484fb998ce31655ff7b45b2021-11-12T12:52:28ZDHAV-1 Blocks the Signaling Pathway Upstream of Type I Interferon by Inhibiting the Interferon Regulatory Factor 7 Protein1664-302X10.3389/fmicb.2021.700434https://doaj.org/article/9217336816484fb998ce31655ff7b45b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.700434/fullhttps://doaj.org/toc/1664-302XDuck hepatitis A virus (DHAV), which mainly infects 1- to 4-week-old ducklings, has a fatality rate of 95% and poses a huge economic threat to the duck industry. However, the mechanism by which DHAV-1 regulates the immune response of host cells is rarely reported. This study examined whether DHAV-1 contains a viral protein that can regulate the innate immunity of host cells and its specific regulatory mechanism, further exploring the mechanism by which DHAV-1 resists the host immune response. In the study, the dual-luciferase reporter gene system was used to screen the viral protein that regulates the host innate immunity and the target of this viral protein. The results indicate that the DHAV-1 3C protein inhibits the pathway upstream of interferon (IFN)-β by targeting the interferon regulatory factor 7 (IRF7) protein. In addition, we found that the 3C protein inhibits the nuclear translocation of the IRF7 protein. Further experiments showed that the 3C protein interacts with the IRF7 protein through its N-terminus and that the 3C protein degrades the IRF7 protein in a caspase 3-dependent manner, thereby inhibiting the IFN-β-mediated antiviral response to promote the replication of DHAV-1. The results of this study are expected to serve as a reference for elucidating the mechanisms of DHAV-1 infection and pathogenicity.Yalan LaiYalan LaiYalan LaiXiaoyan XiaXiaoyan XiaXiaoyan XiaAnchun ChengAnchun ChengAnchun ChengMingshu WangMingshu WangMingshu WangXumin OuXumin OuXumin OuSai MaoSai MaoSai MaoDi SunDi SunDi SunShaqiu ZhangShaqiu ZhangShaqiu ZhangQiao YangQiao YangQiao YangYing WuYing WuYing WuDekang ZhuDekang ZhuRenyong JiaRenyong JiaRenyong JiaShun ChenShun ChenShun ChenMafeng LiuMafeng LiuMafeng LiuXin-Xin ZhaoXin-Xin ZhaoXin-Xin ZhaoJuan HuangJuan HuangJuan HuangQun GaoQun GaoQun GaoBin TianBin TianYunya LiuYunya LiuYunya LiuYanling YuYanling YuYanling YuLing ZhangLing ZhangLing ZhangLeichang PanLeichang PanFrontiers Media S.A.articleduck hepatitis A virus type I3C proteininterferon regulatory factor 7immune regulationtype I interferonMicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021) |
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| topic |
duck hepatitis A virus type I 3C protein interferon regulatory factor 7 immune regulation type I interferon Microbiology QR1-502 |
| spellingShingle |
duck hepatitis A virus type I 3C protein interferon regulatory factor 7 immune regulation type I interferon Microbiology QR1-502 Yalan Lai Yalan Lai Yalan Lai Xiaoyan Xia Xiaoyan Xia Xiaoyan Xia Anchun Cheng Anchun Cheng Anchun Cheng Mingshu Wang Mingshu Wang Mingshu Wang Xumin Ou Xumin Ou Xumin Ou Sai Mao Sai Mao Sai Mao Di Sun Di Sun Di Sun Shaqiu Zhang Shaqiu Zhang Shaqiu Zhang Qiao Yang Qiao Yang Qiao Yang Ying Wu Ying Wu Ying Wu Dekang Zhu Dekang Zhu Renyong Jia Renyong Jia Renyong Jia Shun Chen Shun Chen Shun Chen Mafeng Liu Mafeng Liu Mafeng Liu Xin-Xin Zhao Xin-Xin Zhao Xin-Xin Zhao Juan Huang Juan Huang Juan Huang Qun Gao Qun Gao Qun Gao Bin Tian Bin Tian Yunya Liu Yunya Liu Yunya Liu Yanling Yu Yanling Yu Yanling Yu Ling Zhang Ling Zhang Ling Zhang Leichang Pan Leichang Pan DHAV-1 Blocks the Signaling Pathway Upstream of Type I Interferon by Inhibiting the Interferon Regulatory Factor 7 Protein |
| description |
Duck hepatitis A virus (DHAV), which mainly infects 1- to 4-week-old ducklings, has a fatality rate of 95% and poses a huge economic threat to the duck industry. However, the mechanism by which DHAV-1 regulates the immune response of host cells is rarely reported. This study examined whether DHAV-1 contains a viral protein that can regulate the innate immunity of host cells and its specific regulatory mechanism, further exploring the mechanism by which DHAV-1 resists the host immune response. In the study, the dual-luciferase reporter gene system was used to screen the viral protein that regulates the host innate immunity and the target of this viral protein. The results indicate that the DHAV-1 3C protein inhibits the pathway upstream of interferon (IFN)-β by targeting the interferon regulatory factor 7 (IRF7) protein. In addition, we found that the 3C protein inhibits the nuclear translocation of the IRF7 protein. Further experiments showed that the 3C protein interacts with the IRF7 protein through its N-terminus and that the 3C protein degrades the IRF7 protein in a caspase 3-dependent manner, thereby inhibiting the IFN-β-mediated antiviral response to promote the replication of DHAV-1. The results of this study are expected to serve as a reference for elucidating the mechanisms of DHAV-1 infection and pathogenicity. |
| format |
article |
| author |
Yalan Lai Yalan Lai Yalan Lai Xiaoyan Xia Xiaoyan Xia Xiaoyan Xia Anchun Cheng Anchun Cheng Anchun Cheng Mingshu Wang Mingshu Wang Mingshu Wang Xumin Ou Xumin Ou Xumin Ou Sai Mao Sai Mao Sai Mao Di Sun Di Sun Di Sun Shaqiu Zhang Shaqiu Zhang Shaqiu Zhang Qiao Yang Qiao Yang Qiao Yang Ying Wu Ying Wu Ying Wu Dekang Zhu Dekang Zhu Renyong Jia Renyong Jia Renyong Jia Shun Chen Shun Chen Shun Chen Mafeng Liu Mafeng Liu Mafeng Liu Xin-Xin Zhao Xin-Xin Zhao Xin-Xin Zhao Juan Huang Juan Huang Juan Huang Qun Gao Qun Gao Qun Gao Bin Tian Bin Tian Yunya Liu Yunya Liu Yunya Liu Yanling Yu Yanling Yu Yanling Yu Ling Zhang Ling Zhang Ling Zhang Leichang Pan Leichang Pan |
| author_facet |
Yalan Lai Yalan Lai Yalan Lai Xiaoyan Xia Xiaoyan Xia Xiaoyan Xia Anchun Cheng Anchun Cheng Anchun Cheng Mingshu Wang Mingshu Wang Mingshu Wang Xumin Ou Xumin Ou Xumin Ou Sai Mao Sai Mao Sai Mao Di Sun Di Sun Di Sun Shaqiu Zhang Shaqiu Zhang Shaqiu Zhang Qiao Yang Qiao Yang Qiao Yang Ying Wu Ying Wu Ying Wu Dekang Zhu Dekang Zhu Renyong Jia Renyong Jia Renyong Jia Shun Chen Shun Chen Shun Chen Mafeng Liu Mafeng Liu Mafeng Liu Xin-Xin Zhao Xin-Xin Zhao Xin-Xin Zhao Juan Huang Juan Huang Juan Huang Qun Gao Qun Gao Qun Gao Bin Tian Bin Tian Yunya Liu Yunya Liu Yunya Liu Yanling Yu Yanling Yu Yanling Yu Ling Zhang Ling Zhang Ling Zhang Leichang Pan Leichang Pan |
| author_sort |
Yalan Lai |
| title |
DHAV-1 Blocks the Signaling Pathway Upstream of Type I Interferon by Inhibiting the Interferon Regulatory Factor 7 Protein |
| title_short |
DHAV-1 Blocks the Signaling Pathway Upstream of Type I Interferon by Inhibiting the Interferon Regulatory Factor 7 Protein |
| title_full |
DHAV-1 Blocks the Signaling Pathway Upstream of Type I Interferon by Inhibiting the Interferon Regulatory Factor 7 Protein |
| title_fullStr |
DHAV-1 Blocks the Signaling Pathway Upstream of Type I Interferon by Inhibiting the Interferon Regulatory Factor 7 Protein |
| title_full_unstemmed |
DHAV-1 Blocks the Signaling Pathway Upstream of Type I Interferon by Inhibiting the Interferon Regulatory Factor 7 Protein |
| title_sort |
dhav-1 blocks the signaling pathway upstream of type i interferon by inhibiting the interferon regulatory factor 7 protein |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/9217336816484fb998ce31655ff7b45b |
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