N-linked glycosylation at site 158 of the HA protein of H5N6 highly pathogenic avian influenza virus is important for viral biological properties and host immune responses
Abstract Since 2014, clade 2.3.4.4 has become the dominant epidemic branch of the Asian lineage H5 subtype highly pathogenic avian influenza virus (HPAIV) in southern and eastern China, while the H5N6 subtype is the most prevalent. We have shown earlier that lack of glycosylation at position 158 of...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-01-01
|
| Series: | Veterinary Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13567-020-00879-6 |
| _version_ | 1818959378708955136 |
|---|---|
| author | Ruyi Gao Min Gu Liwei Shi Kaituo Liu Xiuli Li Xiaoquan Wang Jiao Hu Xiaowen Liu Shunlin Hu Sujuan Chen Daxin Peng Xinan Jiao Xiufan Liu |
| author_facet | Ruyi Gao Min Gu Liwei Shi Kaituo Liu Xiuli Li Xiaoquan Wang Jiao Hu Xiaowen Liu Shunlin Hu Sujuan Chen Daxin Peng Xinan Jiao Xiufan Liu |
| author_sort | Ruyi Gao |
| collection | DOAJ |
| description | Abstract Since 2014, clade 2.3.4.4 has become the dominant epidemic branch of the Asian lineage H5 subtype highly pathogenic avian influenza virus (HPAIV) in southern and eastern China, while the H5N6 subtype is the most prevalent. We have shown earlier that lack of glycosylation at position 158 of the hemagglutinin (HA) glycoprotein due to the T160A mutation is a key determinant of the dual receptor binding property of clade 2.3.4.4 H5NX subtypes. Our present study aims to explore other effects of this site among H5N6 viruses. Here we report that N-linked glycosylation at site 158 facilitated the assembly of virus-like particles and enhanced virus replication in A549, MDCK, and chicken embryonic fibroblast (CEF) cells. Consistently, the HA-glycosylated H5N6 virus induced higher levels of inflammatory factors and resulted in stronger pathogenicity in mice than the virus without glycosylation at site 158. However, H5N6 viruses without glycosylation at site 158 were more resistant to heat and bound host cells better than the HA-glycosylated viruses. H5N6 virus without glycosylation at this site triggered the host immune response mechanism to antagonize the viral infection, making viral pathogenicity milder and favoring virus spread. These findings highlight the importance of glycosylation at site 158 of HA for the pathogenicity of the H5N6 viruses. |
| first_indexed | 2024-12-20T11:40:42Z |
| format | Article |
| id | doaj.art-1ca29bcbdfac4d08a36bf77d1a50443f |
| institution | Directory Open Access Journal |
| issn | 1297-9716 |
| language | English |
| last_indexed | 2024-12-20T11:40:42Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj.art-1ca29bcbdfac4d08a36bf77d1a50443f2022-12-21T19:42:00ZengBMCVeterinary Research1297-97162021-01-0152111410.1186/s13567-020-00879-6N-linked glycosylation at site 158 of the HA protein of H5N6 highly pathogenic avian influenza virus is important for viral biological properties and host immune responsesRuyi Gao0Min Gu1Liwei Shi2Kaituo Liu3Xiuli Li4Xiaoquan Wang5Jiao Hu6Xiaowen Liu7Shunlin Hu8Sujuan Chen9Daxin Peng10Xinan Jiao11Xiufan Liu12College of Veterinary Medicine, Yangzhou UniversityCollege of Veterinary Medicine, Yangzhou UniversityCollege of Veterinary Medicine, Yangzhou UniversityCollege of Veterinary Medicine, Yangzhou UniversityCollege of Veterinary Medicine, Yangzhou UniversityCollege of Veterinary Medicine, Yangzhou UniversityCollege of Veterinary Medicine, Yangzhou UniversityCollege of Veterinary Medicine, Yangzhou UniversityCollege of Veterinary Medicine, Yangzhou UniversityCollege of Veterinary Medicine, Yangzhou UniversityCollege of Veterinary Medicine, Yangzhou UniversityCollege of Veterinary Medicine, Yangzhou UniversityCollege of Veterinary Medicine, Yangzhou UniversityAbstract Since 2014, clade 2.3.4.4 has become the dominant epidemic branch of the Asian lineage H5 subtype highly pathogenic avian influenza virus (HPAIV) in southern and eastern China, while the H5N6 subtype is the most prevalent. We have shown earlier that lack of glycosylation at position 158 of the hemagglutinin (HA) glycoprotein due to the T160A mutation is a key determinant of the dual receptor binding property of clade 2.3.4.4 H5NX subtypes. Our present study aims to explore other effects of this site among H5N6 viruses. Here we report that N-linked glycosylation at site 158 facilitated the assembly of virus-like particles and enhanced virus replication in A549, MDCK, and chicken embryonic fibroblast (CEF) cells. Consistently, the HA-glycosylated H5N6 virus induced higher levels of inflammatory factors and resulted in stronger pathogenicity in mice than the virus without glycosylation at site 158. However, H5N6 viruses without glycosylation at site 158 were more resistant to heat and bound host cells better than the HA-glycosylated viruses. H5N6 virus without glycosylation at this site triggered the host immune response mechanism to antagonize the viral infection, making viral pathogenicity milder and favoring virus spread. These findings highlight the importance of glycosylation at site 158 of HA for the pathogenicity of the H5N6 viruses.https://doi.org/10.1186/s13567-020-00879-6H5N6 avian influenza virusglycosylationpathogenicityhost immune response |
| spellingShingle | Ruyi Gao Min Gu Liwei Shi Kaituo Liu Xiuli Li Xiaoquan Wang Jiao Hu Xiaowen Liu Shunlin Hu Sujuan Chen Daxin Peng Xinan Jiao Xiufan Liu N-linked glycosylation at site 158 of the HA protein of H5N6 highly pathogenic avian influenza virus is important for viral biological properties and host immune responses Veterinary Research H5N6 avian influenza virus glycosylation pathogenicity host immune response |
| title | N-linked glycosylation at site 158 of the HA protein of H5N6 highly pathogenic avian influenza virus is important for viral biological properties and host immune responses |
| title_full | N-linked glycosylation at site 158 of the HA protein of H5N6 highly pathogenic avian influenza virus is important for viral biological properties and host immune responses |
| title_fullStr | N-linked glycosylation at site 158 of the HA protein of H5N6 highly pathogenic avian influenza virus is important for viral biological properties and host immune responses |
| title_full_unstemmed | N-linked glycosylation at site 158 of the HA protein of H5N6 highly pathogenic avian influenza virus is important for viral biological properties and host immune responses |
| title_short | N-linked glycosylation at site 158 of the HA protein of H5N6 highly pathogenic avian influenza virus is important for viral biological properties and host immune responses |
| title_sort | n linked glycosylation at site 158 of the ha protein of h5n6 highly pathogenic avian influenza virus is important for viral biological properties and host immune responses |
| topic | H5N6 avian influenza virus glycosylation pathogenicity host immune response |
| url | https://doi.org/10.1186/s13567-020-00879-6 |
| work_keys_str_mv | AT ruyigao nlinkedglycosylationatsite158ofthehaproteinofh5n6highlypathogenicavianinfluenzavirusisimportantforviralbiologicalpropertiesandhostimmuneresponses AT mingu nlinkedglycosylationatsite158ofthehaproteinofh5n6highlypathogenicavianinfluenzavirusisimportantforviralbiologicalpropertiesandhostimmuneresponses AT liweishi nlinkedglycosylationatsite158ofthehaproteinofh5n6highlypathogenicavianinfluenzavirusisimportantforviralbiologicalpropertiesandhostimmuneresponses AT kaituoliu nlinkedglycosylationatsite158ofthehaproteinofh5n6highlypathogenicavianinfluenzavirusisimportantforviralbiologicalpropertiesandhostimmuneresponses AT xiulili nlinkedglycosylationatsite158ofthehaproteinofh5n6highlypathogenicavianinfluenzavirusisimportantforviralbiologicalpropertiesandhostimmuneresponses AT xiaoquanwang nlinkedglycosylationatsite158ofthehaproteinofh5n6highlypathogenicavianinfluenzavirusisimportantforviralbiologicalpropertiesandhostimmuneresponses AT jiaohu nlinkedglycosylationatsite158ofthehaproteinofh5n6highlypathogenicavianinfluenzavirusisimportantforviralbiologicalpropertiesandhostimmuneresponses AT xiaowenliu nlinkedglycosylationatsite158ofthehaproteinofh5n6highlypathogenicavianinfluenzavirusisimportantforviralbiologicalpropertiesandhostimmuneresponses AT shunlinhu nlinkedglycosylationatsite158ofthehaproteinofh5n6highlypathogenicavianinfluenzavirusisimportantforviralbiologicalpropertiesandhostimmuneresponses AT sujuanchen nlinkedglycosylationatsite158ofthehaproteinofh5n6highlypathogenicavianinfluenzavirusisimportantforviralbiologicalpropertiesandhostimmuneresponses AT daxinpeng nlinkedglycosylationatsite158ofthehaproteinofh5n6highlypathogenicavianinfluenzavirusisimportantforviralbiologicalpropertiesandhostimmuneresponses AT xinanjiao nlinkedglycosylationatsite158ofthehaproteinofh5n6highlypathogenicavianinfluenzavirusisimportantforviralbiologicalpropertiesandhostimmuneresponses AT xiufanliu nlinkedglycosylationatsite158ofthehaproteinofh5n6highlypathogenicavianinfluenzavirusisimportantforviralbiologicalpropertiesandhostimmuneresponses |