Billington Elizabeth, Di Genova Cecilia, Warren Caroline J, Thomas Saumya S, Johnson Simon, Riccio Sofia, De Silva Dilhani, Peers-Dent Jacob, Temperton Nigel, da Costa Kelly, Byrne Alexander M P, Airey Maisie, Schlachter Audra-Lynne, Yang Jiayun, Nunez Alejandro, Iqbal Munir, Slomka Marek J, Brown Ian H, Banyard Ashley C, James Joe
Influenza and Avian Virology Workgroup, Department of Virology, Animal and Plant Health Agency (APHA-Weybridge), Woodham Lane, Addlestone, Surrey KT15 3NB, UK.
Viral Pseudotype Unit, Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, Kent ME4 4TB, UK.
J Gen Virol. 2025 Sep;106(9). doi: 10.1099/jgv.0.002150.
H5Nx clade 2.3.4.4b high pathogenicity avian influenza viruses (HPAIVs) have decimated wild bird and poultry populations globally since the autumn of 2020. In the UK and in continental Europe, the H5N8 subtype predominated during the first epizootic wave of 2020/21, with few detections of H5N1. However, during the second (2021/22) and third (2022/23) epizootic waves, H5N1 was the dominant subtype. The rapid shift in dominance from H5N8 to H5N1 was likely driven by a combination of virological, immunological and/or host-related factors. In this study, we compared viral fitness and immunological responses in ducks, a key reservoir species, using dominant genotypes of H5N1 (genotype AB) and H5N8 (genotype A) from the second wave. While viral shedding dynamics were similar for both viruses, H5N8 was more pathogenic. Antigenic analysis of post-infection duck sera revealed that the haemagglutinin protein was antigenically similar across clade 2.3.4.4b H5 HPAIVs, but neuraminidase proteins displayed different patterns of cross-reactivity. We also modelled a scenario where ducks were pre-exposed to H5N1 (genotype C) or H5N8 (genotype A) from the first wave and subsequently challenged with either homologous or heterologous subtypes from the second wave (genotype AB or A). Despite the absence of seroconversion, pre-exposure to different subtypes resulted in varying clinical outcomes following challenge. These findings indicate that both viral and immunological factors likely played significant roles in the emergence and spread of H5Nx HPAIVs in wild bird populations.
自2020年秋季以来，H5Nx进化分支2.3.4.4b高致病性禽流感病毒（HPAIVs）已使全球野生鸟类和家禽数量大幅减少。在英国和欧洲大陆，H5N8亚型在2020/21年的第一波动物疫情中占主导地位，H5N1的检测数量很少。然而，在第二波（2021/22年）和第三波（2022/23年）动物疫情中，H5N1成为了主要亚型。从H5N8到H5N1的优势迅速转变可能是由病毒学、免疫学和/或宿主相关因素共同驱动的。在本研究中，我们使用第二波疫情中的H5N1优势基因型（AB型）和H5N8优势基因型（A型），比较了关键宿主物种鸭子的病毒适应性和免疫反应。虽然两种病毒的病毒脱落动态相似，但H5N8的致病性更强。感染后鸭血清的抗原分析表明，2.3.4.4b进化分支H5 HPAIVs的血凝素蛋白在抗原性上相似，但神经氨酸酶蛋白显示出不同的交叉反应模式。我们还模拟了一种情况，即鸭子预先接触第一波疫情中的H5N1（C型）或H5N8（A型），随后用第二波疫情中的同源或异源亚型（AB型或A型）进行攻毒。尽管没有发生血清转化，但预先接触不同亚型会导致攻毒后出现不同的临床结果。这些发现表明，病毒和免疫因素可能在H5Nx HPAIVs在野生鸟类种群中的出现和传播中都发挥了重要作用。
