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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Main Authors: Huizi Li, Shishi Wang, Ruihong Guo, Xijiao Chen, Yuanyuan Huang, Weixin Jia, Zhangyong Ning
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Poultry Science
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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
issn 0032-5791
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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