GGCX promotes Eurasian avian-like H1N1 swine influenza virus adaption to interspecies receptor binding
Abstract The Eurasian avian-like (EA) H1N1 swine influenza virus (SIV) possesses the capacity to instigate the next influenza pandemic, owing to its heightened affinity for the human-type α-2,6 sialic acid (SA) receptor. Nevertheless, the molecular mechanisms underlying the switch in receptor bindin...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55903-0 |
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| author | Jiahui Zou Meijun Jiang Rong Xiao Huimin Sun Hailong Liu Thomas Peacock Shaoyu Tu Tong Chen Jinli Guo Yaxin Zhao Wendy Barclay Shengsong Xie Hongbo Zhou |
| author_facet | Jiahui Zou Meijun Jiang Rong Xiao Huimin Sun Hailong Liu Thomas Peacock Shaoyu Tu Tong Chen Jinli Guo Yaxin Zhao Wendy Barclay Shengsong Xie Hongbo Zhou |
| author_sort | Jiahui Zou |
| collection | DOAJ |
| description | Abstract The Eurasian avian-like (EA) H1N1 swine influenza virus (SIV) possesses the capacity to instigate the next influenza pandemic, owing to its heightened affinity for the human-type α-2,6 sialic acid (SA) receptor. Nevertheless, the molecular mechanisms underlying the switch in receptor binding preferences of EA H1N1 SIV remain elusive. In this study, we conduct a comprehensive genome-wide CRISPR/Cas9 knockout screen utilizing EA H1N1 SIV in porcine kidney cells. Knocking out the enzyme gamma glutamyl carboxylase (GGCX) reduces virus replication in vitro and in vivo by inhibiting the carboxylation modification of viral haemagglutinin (HA) and the adhesion of progeny viruses, ultimately impeding the replication of EA H1N1 SIV. Furthermore, GGCX is revealed to be the determinant of the D225E substitution of EA H1N1 SIV, and GGCX-medicated carboxylation modification of HA 225E contributes to the receptor binding adaption of EA H1N1 SIV to the α-2,6 SA receptor. Taken together, our CRISPR screen has elucidated a novel function of GGCX in the support of EA H1N1 SIV adaption for binding to α-2,6 SA receptor. Consequently, GGCX emerges as a prospective antiviral target against the infection and transmission of EA H1N1 SIV. |
| format | Article |
| id | doaj-art-3212f5273fae48efa8e83e8443f26515 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-3212f5273fae48efa8e83e8443f265152025-01-19T12:30:29ZengNature PortfolioNature Communications2041-17232025-01-0116111410.1038/s41467-025-55903-0GGCX promotes Eurasian avian-like H1N1 swine influenza virus adaption to interspecies receptor bindingJiahui Zou0Meijun Jiang1Rong Xiao2Huimin Sun3Hailong Liu4Thomas Peacock5Shaoyu Tu6Tong Chen7Jinli Guo8Yaxin Zhao9Wendy Barclay10Shengsong Xie11Hongbo Zhou12National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Lab of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural UniversityDepartment of Infectious Disease, Imperial College LondonNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityDepartment of Infectious Disease, Imperial College LondonKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Lab of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural UniversityNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityAbstract The Eurasian avian-like (EA) H1N1 swine influenza virus (SIV) possesses the capacity to instigate the next influenza pandemic, owing to its heightened affinity for the human-type α-2,6 sialic acid (SA) receptor. Nevertheless, the molecular mechanisms underlying the switch in receptor binding preferences of EA H1N1 SIV remain elusive. In this study, we conduct a comprehensive genome-wide CRISPR/Cas9 knockout screen utilizing EA H1N1 SIV in porcine kidney cells. Knocking out the enzyme gamma glutamyl carboxylase (GGCX) reduces virus replication in vitro and in vivo by inhibiting the carboxylation modification of viral haemagglutinin (HA) and the adhesion of progeny viruses, ultimately impeding the replication of EA H1N1 SIV. Furthermore, GGCX is revealed to be the determinant of the D225E substitution of EA H1N1 SIV, and GGCX-medicated carboxylation modification of HA 225E contributes to the receptor binding adaption of EA H1N1 SIV to the α-2,6 SA receptor. Taken together, our CRISPR screen has elucidated a novel function of GGCX in the support of EA H1N1 SIV adaption for binding to α-2,6 SA receptor. Consequently, GGCX emerges as a prospective antiviral target against the infection and transmission of EA H1N1 SIV.https://doi.org/10.1038/s41467-025-55903-0 |
| spellingShingle | Jiahui Zou Meijun Jiang Rong Xiao Huimin Sun Hailong Liu Thomas Peacock Shaoyu Tu Tong Chen Jinli Guo Yaxin Zhao Wendy Barclay Shengsong Xie Hongbo Zhou GGCX promotes Eurasian avian-like H1N1 swine influenza virus adaption to interspecies receptor binding Nature Communications |
| title | GGCX promotes Eurasian avian-like H1N1 swine influenza virus adaption to interspecies receptor binding |
| title_full | GGCX promotes Eurasian avian-like H1N1 swine influenza virus adaption to interspecies receptor binding |
| title_fullStr | GGCX promotes Eurasian avian-like H1N1 swine influenza virus adaption to interspecies receptor binding |
| title_full_unstemmed | GGCX promotes Eurasian avian-like H1N1 swine influenza virus adaption to interspecies receptor binding |
| title_short | GGCX promotes Eurasian avian-like H1N1 swine influenza virus adaption to interspecies receptor binding |
| title_sort | ggcx promotes eurasian avian like h1n1 swine influenza virus adaption to interspecies receptor binding |
| url | https://doi.org/10.1038/s41467-025-55903-0 |
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