E627V mutation in PB2 protein promotes the mammalian adaptation of novel H10N3 avian influenza virus

Abstract Since 2021, the novel H10N3 has caused four cases of human infection in China, the most recent of which occurred in December 2024, posing a potential threat to public health. Our previous studies indicated that several avian H10N3 strains are highly pathogenic in mice and can be transmitted...

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Main Authors: Meishan Song, Jianyu Liang, Sige Wang, Ruyi Gao, Xiaolong Lu, Wenhao Yang, Yu Chen, Jingxia Ma, Min Gu, Jiao Hu, Xiaowen Liu, Shunlin Hu, Xiaoquan Wang, Kaituo Liu, Xiufan Liu
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Veterinary Research
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Online Access:https://doi.org/10.1186/s13567-025-01534-8
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author Meishan Song
Jianyu Liang
Sige Wang
Ruyi Gao
Xiaolong Lu
Wenhao Yang
Yu Chen
Jingxia Ma
Min Gu
Jiao Hu
Xiaowen Liu
Shunlin Hu
Xiaoquan Wang
Kaituo Liu
Xiufan Liu
author_facet Meishan Song
Jianyu Liang
Sige Wang
Ruyi Gao
Xiaolong Lu
Wenhao Yang
Yu Chen
Jingxia Ma
Min Gu
Jiao Hu
Xiaowen Liu
Shunlin Hu
Xiaoquan Wang
Kaituo Liu
Xiufan Liu
author_sort Meishan Song
collection DOAJ
description Abstract Since 2021, the novel H10N3 has caused four cases of human infection in China, the most recent of which occurred in December 2024, posing a potential threat to public health. Our previous studies indicated that several avian H10N3 strains are highly pathogenic in mice and can be transmitted between mammals via respiratory droplets without prior adaptation. By analyzing the genome sequence, we found that these H10N3 viruses carry the PB2-E627V mutation, which is becoming increasingly common in several subtypes of avian influenza viruses (AIV); however, its mechanism in mammalian adaptation remains unclear. Using a reverse genetics system, we investigated the role of PB2-E627V in the adaptation of H10N3 to mammals and poultry. Our findings demonstrate that the PB2-E627V mutation is critical for the high pathogenicity of novel H10N3 in mice and its ability to be transmitted through the air among mammals. Additionally, we found that the role of PB2-627 V in promoting AIV adaptation to mammals is comparable to that of PB2-627 K. More importantly, PB2-627 V appears to be equally suited to long-term persistence in poultry. Therefore, using PB2-627 V as a novel molecular marker to assess the epidemic potential of AIV is of great significance for preventing possible influenza pandemics in the future.
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publishDate 2025-06-01
publisher BMC
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series Veterinary Research
spelling doaj-art-8439d6f18d504ca7a3978b4c3dbbbd942025-08-20T02:30:43ZengBMCVeterinary Research1297-97162025-06-0156111410.1186/s13567-025-01534-8E627V mutation in PB2 protein promotes the mammalian adaptation of novel H10N3 avian influenza virusMeishan Song0Jianyu Liang1Sige Wang2Ruyi Gao3Xiaolong Lu4Wenhao Yang5Yu Chen6Jingxia Ma7Min Gu8Jiao Hu9Xiaowen Liu10Shunlin Hu11Xiaoquan Wang12Kaituo Liu13Xiufan Liu14Key Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, Yangzhou UniversityKey Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, Yangzhou UniversityKey Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, Yangzhou UniversityKey Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, Yangzhou UniversityKey Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, Yangzhou UniversityKey Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, Yangzhou UniversityKey Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, Yangzhou UniversityBinzhou Argo-Tech Extension CenterKey Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, Yangzhou UniversityKey Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, Yangzhou UniversityKey Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, Yangzhou UniversityKey Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, Yangzhou UniversityJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, College of Veterinary Medicine, Yangzhou UniversityJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, College of Veterinary Medicine, Yangzhou UniversityJoint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, College of Veterinary Medicine, Yangzhou UniversityAbstract Since 2021, the novel H10N3 has caused four cases of human infection in China, the most recent of which occurred in December 2024, posing a potential threat to public health. Our previous studies indicated that several avian H10N3 strains are highly pathogenic in mice and can be transmitted between mammals via respiratory droplets without prior adaptation. By analyzing the genome sequence, we found that these H10N3 viruses carry the PB2-E627V mutation, which is becoming increasingly common in several subtypes of avian influenza viruses (AIV); however, its mechanism in mammalian adaptation remains unclear. Using a reverse genetics system, we investigated the role of PB2-E627V in the adaptation of H10N3 to mammals and poultry. Our findings demonstrate that the PB2-E627V mutation is critical for the high pathogenicity of novel H10N3 in mice and its ability to be transmitted through the air among mammals. Additionally, we found that the role of PB2-627 V in promoting AIV adaptation to mammals is comparable to that of PB2-627 K. More importantly, PB2-627 V appears to be equally suited to long-term persistence in poultry. Therefore, using PB2-627 V as a novel molecular marker to assess the epidemic potential of AIV is of great significance for preventing possible influenza pandemics in the future.https://doi.org/10.1186/s13567-025-01534-8Avian influenza virusnovel H10N3mammal adaptionPB2-E627V/K
spellingShingle Meishan Song
Jianyu Liang
Sige Wang
Ruyi Gao
Xiaolong Lu
Wenhao Yang
Yu Chen
Jingxia Ma
Min Gu
Jiao Hu
Xiaowen Liu
Shunlin Hu
Xiaoquan Wang
Kaituo Liu
Xiufan Liu
E627V mutation in PB2 protein promotes the mammalian adaptation of novel H10N3 avian influenza virus
Veterinary Research
Avian influenza virus
novel H10N3
mammal adaption
PB2-E627V/K
title E627V mutation in PB2 protein promotes the mammalian adaptation of novel H10N3 avian influenza virus
title_full E627V mutation in PB2 protein promotes the mammalian adaptation of novel H10N3 avian influenza virus
title_fullStr E627V mutation in PB2 protein promotes the mammalian adaptation of novel H10N3 avian influenza virus
title_full_unstemmed E627V mutation in PB2 protein promotes the mammalian adaptation of novel H10N3 avian influenza virus
title_short E627V mutation in PB2 protein promotes the mammalian adaptation of novel H10N3 avian influenza virus
title_sort e627v mutation in pb2 protein promotes the mammalian adaptation of novel h10n3 avian influenza virus
topic Avian influenza virus
novel H10N3
mammal adaption
PB2-E627V/K
url https://doi.org/10.1186/s13567-025-01534-8
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