Isoleucine at position 137 of haemagglutinin acts as a mammalian adaptation marker of H9N2 avian influenza virus

The H9N2 subtype of avian influenza virus (AIV) is widely distributed among poultry and wild birds and is also a threat to humans. During AIV active surveillance in Liaoning province from 2015 to 2016, we identified 10 H9N2 strains exhibiting different lethality to chick embryos. Two representative...

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Main Authors: Weiwei Ma, Chenyang Ren, Lin Shi, Bo Meng, Yali Feng, Ying Zhang
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2025.2455597
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author Weiwei Ma
Chenyang Ren
Lin Shi
Bo Meng
Yali Feng
Ying Zhang
author_facet Weiwei Ma
Chenyang Ren
Lin Shi
Bo Meng
Yali Feng
Ying Zhang
author_sort Weiwei Ma
collection DOAJ
description The H9N2 subtype of avian influenza virus (AIV) is widely distributed among poultry and wild birds and is also a threat to humans. During AIV active surveillance in Liaoning province from 2015 to 2016, we identified 10 H9N2 strains exhibiting different lethality to chick embryos. Two representative strains, A/chicken/China/LN07/2016 (CKLN/07) and A/chicken/China/LN17/2016 (CKLN/17), with similar genomic background but different chick embryo lethality, were chosen to evaluate the molecular basis for this difference. A series of reassortants between CKLN/07 and CKLN/17 were generated and their chick embryo lethality was assessed. We found that the isoleucine (I) residue at position 137 (H3 numbering) in the haemagglutinin (HA) was responsible for the chick embryo lethality of the H9N2 virus. Further studies revealed that the threonine (T) to I mutation at HA position 137 enhanced viral replication in vitro and in vivo. Moreover, the HA-T137I substitution in H9N2 avian influenza virus increased the guinea pig transmission efficiency. We also found that the HA-T137I substitution was critical for α2,6-linked sialic acid binding preference and HA activation and stability of H9N2 virus. Our findings demonstrated that HA-137I is a key molecular marker for mammalian adaptation of H9N2 AIV.
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spelling doaj-art-fa756c301a284ccbae37a10f262d83142025-01-31T16:23:48ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512025-12-0114110.1080/22221751.2025.2455597Isoleucine at position 137 of haemagglutinin acts as a mammalian adaptation marker of H9N2 avian influenza virusWeiwei Ma0Chenyang Ren1Lin Shi2Bo Meng3Yali Feng4Ying Zhang5Key Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, Shenyang Agricultural University, Shenyang, People’s Republic of ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, Shenyang Agricultural University, Shenyang, People’s Republic of ChinaPoultry Diseases Research Laboratory, Liaoning Center for Prevention and Control of Animal Infectious Diseases, Shenyang, People’s Republic of ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, Shenyang Agricultural University, Shenyang, People’s Republic of ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, Shenyang Agricultural University, Shenyang, People’s Republic of ChinaKey Laboratory of Livestock Infectious Diseases, Ministry of Education, Key Laboratory of Zoonosis, College of Animal Science and Veterinary Medicine, Liaoning Panjin Wetland Ecosystem National Observation and Research Station, Shenyang Agricultural University, Shenyang, People’s Republic of ChinaThe H9N2 subtype of avian influenza virus (AIV) is widely distributed among poultry and wild birds and is also a threat to humans. During AIV active surveillance in Liaoning province from 2015 to 2016, we identified 10 H9N2 strains exhibiting different lethality to chick embryos. Two representative strains, A/chicken/China/LN07/2016 (CKLN/07) and A/chicken/China/LN17/2016 (CKLN/17), with similar genomic background but different chick embryo lethality, were chosen to evaluate the molecular basis for this difference. A series of reassortants between CKLN/07 and CKLN/17 were generated and their chick embryo lethality was assessed. We found that the isoleucine (I) residue at position 137 (H3 numbering) in the haemagglutinin (HA) was responsible for the chick embryo lethality of the H9N2 virus. Further studies revealed that the threonine (T) to I mutation at HA position 137 enhanced viral replication in vitro and in vivo. Moreover, the HA-T137I substitution in H9N2 avian influenza virus increased the guinea pig transmission efficiency. We also found that the HA-T137I substitution was critical for α2,6-linked sialic acid binding preference and HA activation and stability of H9N2 virus. Our findings demonstrated that HA-137I is a key molecular marker for mammalian adaptation of H9N2 AIV.https://www.tandfonline.com/doi/10.1080/22221751.2025.2455597Avian influenza virusH9N2haemagglutininreceptor-binding propertystability
spellingShingle Weiwei Ma
Chenyang Ren
Lin Shi
Bo Meng
Yali Feng
Ying Zhang
Isoleucine at position 137 of haemagglutinin acts as a mammalian adaptation marker of H9N2 avian influenza virus
Emerging Microbes and Infections
Avian influenza virus
H9N2
haemagglutinin
receptor-binding property
stability
title Isoleucine at position 137 of haemagglutinin acts as a mammalian adaptation marker of H9N2 avian influenza virus
title_full Isoleucine at position 137 of haemagglutinin acts as a mammalian adaptation marker of H9N2 avian influenza virus
title_fullStr Isoleucine at position 137 of haemagglutinin acts as a mammalian adaptation marker of H9N2 avian influenza virus
title_full_unstemmed Isoleucine at position 137 of haemagglutinin acts as a mammalian adaptation marker of H9N2 avian influenza virus
title_short Isoleucine at position 137 of haemagglutinin acts as a mammalian adaptation marker of H9N2 avian influenza virus
title_sort isoleucine at position 137 of haemagglutinin acts as a mammalian adaptation marker of h9n2 avian influenza virus
topic Avian influenza virus
H9N2
haemagglutinin
receptor-binding property
stability
url https://www.tandfonline.com/doi/10.1080/22221751.2025.2455597
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