Wild Bird-Origin H6N2 Influenza Virus Acquires Enhanced Pathogenicity after Single Passage in Mice
The H6 subtype of avian influenza viruses (AIVs) has emerged as one of the predominant subtypes in both wild and domestic avian species. Currently, H6 AIVs have acquired the ability to infect a wide range of mammals, though the related molecular mechanisms have yet to be fully investigated. In this...
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MDPI AG
2024-02-01
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| author | Siqi Tang Bing Han Chaofan Su Hailing Li Shiyuchen Zhao Haoyu Leng Yali Feng Ying Zhang |
| author_facet | Siqi Tang Bing Han Chaofan Su Hailing Li Shiyuchen Zhao Haoyu Leng Yali Feng Ying Zhang |
| author_sort | Siqi Tang |
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| description | The H6 subtype of avian influenza viruses (AIVs) has emerged as one of the predominant subtypes in both wild and domestic avian species. Currently, H6 AIVs have acquired the ability to infect a wide range of mammals, though the related molecular mechanisms have yet to be fully investigated. In this study, a wild bird-origin H6N2 AIV was isolated from the East Asian–Australasian migratory flyway region located in Liaoning Province. This H6N2 virus initially expressed limited replication in mice. However, after one passage in mice, the virus acquired two mutations, PB2 E627K and HA A110V. The mutant displayed enhanced replication both in vitro and in vivo, proving lethal to mice. But the mutant retained the α-2, 3-linked sialic acid binding property and failed to transmit in guinea pigs. We explored the molecular mechanisms underlying the pathogenicity difference between the wild type and the mutant. Our findings revealed that PB2 E627K dramatically enhanced the polymerase activity of the H6N2 virus, while the HA A110V mutation decreased the pH of HA activation. This study demonstrated that the H6N2 subtype wild bird-origin AIV easily acquired the mammalian adaptation. The monitoring and evaluation of H6 wild bird-origin AIV should be strengthened. |
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| issn | 1999-4915 |
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| spelling | doaj.art-24cf988351ad4e46be4562a2b99a4aaf2024-03-27T14:07:39ZengMDPI AGViruses1999-49152024-02-0116335710.3390/v16030357Wild Bird-Origin H6N2 Influenza Virus Acquires Enhanced Pathogenicity after Single Passage in MiceSiqi Tang0Bing Han1Chaofan Su2Hailing Li3Shiyuchen Zhao4Haoyu Leng5Yali Feng6Ying Zhang7Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Rd., Shenyang 110866, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Rd., Shenyang 110866, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Rd., Shenyang 110866, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Rd., Shenyang 110866, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Rd., Shenyang 110866, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Rd., Shenyang 110866, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Rd., Shenyang 110866, ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, Laboratory of Ruminant Infectious Disease Prevention and Control (East), Ministry of Agriculture and Rural Affairs, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, 120 Dongling Rd., Shenyang 110866, ChinaThe H6 subtype of avian influenza viruses (AIVs) has emerged as one of the predominant subtypes in both wild and domestic avian species. Currently, H6 AIVs have acquired the ability to infect a wide range of mammals, though the related molecular mechanisms have yet to be fully investigated. In this study, a wild bird-origin H6N2 AIV was isolated from the East Asian–Australasian migratory flyway region located in Liaoning Province. This H6N2 virus initially expressed limited replication in mice. However, after one passage in mice, the virus acquired two mutations, PB2 E627K and HA A110V. The mutant displayed enhanced replication both in vitro and in vivo, proving lethal to mice. But the mutant retained the α-2, 3-linked sialic acid binding property and failed to transmit in guinea pigs. We explored the molecular mechanisms underlying the pathogenicity difference between the wild type and the mutant. Our findings revealed that PB2 E627K dramatically enhanced the polymerase activity of the H6N2 virus, while the HA A110V mutation decreased the pH of HA activation. This study demonstrated that the H6N2 subtype wild bird-origin AIV easily acquired the mammalian adaptation. The monitoring and evaluation of H6 wild bird-origin AIV should be strengthened.https://www.mdpi.com/1999-4915/16/3/357wild bird-origin influenza virusenhancedadaptationpathogenicity |
| spellingShingle | Siqi Tang Bing Han Chaofan Su Hailing Li Shiyuchen Zhao Haoyu Leng Yali Feng Ying Zhang Wild Bird-Origin H6N2 Influenza Virus Acquires Enhanced Pathogenicity after Single Passage in Mice Viruses wild bird-origin influenza virus enhanced adaptation pathogenicity |
| title | Wild Bird-Origin H6N2 Influenza Virus Acquires Enhanced Pathogenicity after Single Passage in Mice |
| title_full | Wild Bird-Origin H6N2 Influenza Virus Acquires Enhanced Pathogenicity after Single Passage in Mice |
| title_fullStr | Wild Bird-Origin H6N2 Influenza Virus Acquires Enhanced Pathogenicity after Single Passage in Mice |
| title_full_unstemmed | Wild Bird-Origin H6N2 Influenza Virus Acquires Enhanced Pathogenicity after Single Passage in Mice |
| title_short | Wild Bird-Origin H6N2 Influenza Virus Acquires Enhanced Pathogenicity after Single Passage in Mice |
| title_sort | wild bird origin h6n2 influenza virus acquires enhanced pathogenicity after single passage in mice |
| topic | wild bird-origin influenza virus enhanced adaptation pathogenicity |
| url | https://www.mdpi.com/1999-4915/16/3/357 |
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