Chicken C4BPM facilitates replication of H5N1 and H9N2 Avian Influenza Viruses by inhibiting the production of type I interferons
Avian influenza viruses (AIVs) are potential pandemic of global concern, posing a major threat to both the poultry industry and human health. Host factors play a key role in the replication of AIVs, while the function of complement component 4 binding protein, membrane (C4BPM) in this process is sti...
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Elsevier
2025-03-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0032579125001051 |
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author | Huizi Li Shishi Wang Ruihong Guo Xijiao Chen Yuanyuan Huang Weixin Jia Zhangyong Ning |
author_facet | Huizi Li Shishi Wang Ruihong Guo Xijiao Chen Yuanyuan Huang Weixin Jia Zhangyong Ning |
author_sort | Huizi Li |
collection | DOAJ |
description | Avian influenza viruses (AIVs) are potential pandemic of global concern, posing a major threat to both the poultry industry and human health. Host factors play a key role in the replication of AIVs, while the function of complement component 4 binding protein, membrane (C4BPM) in this process is still unclear. This research reports that C4BPM promotes replication of H5N1 and H9N2 AIVs by inhibiting type I interferons (IFNs). H5N1 and H9N2 AIVs infection up-regulate the expression of C4BPM in chicken embryo fibroblast cells (DF-1). To verify the role of C4BPM in replication of AIVs, C4BPM knockout (C4BPM-KO) and stable overexpressing (C4BPM-overexpressing) DF-1 cells were generated using lentivirus-mediated CRISPR/Cas9 gene editing technology and molecular cloning strategies. Replication of H5N1 and H9N2 AIVs were promoted in C4BPM-overexpressing DF-1 cells with inhibited expression of type I IFNs (IFN-α, IFN-β), protein kinase R (PKR), cholesterol 25-hydroxylase (CH25H), interferon regulatory factor (IRF) 3, and mitochondrial antiviral signaling protein (MAVS) compared to that of the DF-1 cells. However, the replication of H5N1 and H9N2 AIVs in C4BPM-KO DF-1 cells were inhibited with the increased expression of above related anti-viral factors. Further results showed that C4BPM did not affect viral adsorption, while, promote the entry of H5N1 and H9N2 AIVs. These results expand the range of host factors regulating replication of AIVs and suggest that C4BPM is a promising target for anti-viral agent. |
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institution | Kabale University |
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language | English |
publishDate | 2025-03-01 |
publisher | Elsevier |
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series | Poultry Science |
spelling | doaj-art-5171ebb268aa4beeb1474571e01acbbb2025-02-06T05:10:55ZengElsevierPoultry Science0032-57912025-03-011043104868Chicken C4BPM facilitates replication of H5N1 and H9N2 Avian Influenza Viruses by inhibiting the production of type I interferonsHuizi Li0Shishi Wang1Ruihong Guo2Xijiao Chen3Yuanyuan Huang4Weixin Jia5Zhangyong Ning6College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, PR ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, PR ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, PR ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, PR ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, PR ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, PR ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, PR China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Maoming, 525000, PR China; Corresponding author.Avian influenza viruses (AIVs) are potential pandemic of global concern, posing a major threat to both the poultry industry and human health. Host factors play a key role in the replication of AIVs, while the function of complement component 4 binding protein, membrane (C4BPM) in this process is still unclear. This research reports that C4BPM promotes replication of H5N1 and H9N2 AIVs by inhibiting type I interferons (IFNs). H5N1 and H9N2 AIVs infection up-regulate the expression of C4BPM in chicken embryo fibroblast cells (DF-1). To verify the role of C4BPM in replication of AIVs, C4BPM knockout (C4BPM-KO) and stable overexpressing (C4BPM-overexpressing) DF-1 cells were generated using lentivirus-mediated CRISPR/Cas9 gene editing technology and molecular cloning strategies. Replication of H5N1 and H9N2 AIVs were promoted in C4BPM-overexpressing DF-1 cells with inhibited expression of type I IFNs (IFN-α, IFN-β), protein kinase R (PKR), cholesterol 25-hydroxylase (CH25H), interferon regulatory factor (IRF) 3, and mitochondrial antiviral signaling protein (MAVS) compared to that of the DF-1 cells. However, the replication of H5N1 and H9N2 AIVs in C4BPM-KO DF-1 cells were inhibited with the increased expression of above related anti-viral factors. Further results showed that C4BPM did not affect viral adsorption, while, promote the entry of H5N1 and H9N2 AIVs. These results expand the range of host factors regulating replication of AIVs and suggest that C4BPM is a promising target for anti-viral agent.http://www.sciencedirect.com/science/article/pii/S0032579125001051Avian influenza virusC4BPMDF-1ReplicationIFNs |
spellingShingle | Huizi Li Shishi Wang Ruihong Guo Xijiao Chen Yuanyuan Huang Weixin Jia Zhangyong Ning Chicken C4BPM facilitates replication of H5N1 and H9N2 Avian Influenza Viruses by inhibiting the production of type I interferons Poultry Science Avian influenza virus C4BPM DF-1 Replication IFNs |
title | Chicken C4BPM facilitates replication of H5N1 and H9N2 Avian Influenza Viruses by inhibiting the production of type I interferons |
title_full | Chicken C4BPM facilitates replication of H5N1 and H9N2 Avian Influenza Viruses by inhibiting the production of type I interferons |
title_fullStr | Chicken C4BPM facilitates replication of H5N1 and H9N2 Avian Influenza Viruses by inhibiting the production of type I interferons |
title_full_unstemmed | Chicken C4BPM facilitates replication of H5N1 and H9N2 Avian Influenza Viruses by inhibiting the production of type I interferons |
title_short | Chicken C4BPM facilitates replication of H5N1 and H9N2 Avian Influenza Viruses by inhibiting the production of type I interferons |
title_sort | chicken c4bpm facilitates replication of h5n1 and h9n2 avian influenza viruses by inhibiting the production of type i interferons |
topic | Avian influenza virus C4BPM DF-1 Replication IFNs |
url | http://www.sciencedirect.com/science/article/pii/S0032579125001051 |
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