Song Meishan, Liang Jianyu, Wang Sige, Gao Ruyi, Lu Xiaolong, Yang Wenhao, Chen Yu, Ma Jingxia, Gu Min, Hu Jiao, Liu Xiaowen, Hu Shunlin, Wang Xiaoquan, Liu Kaituo, Liu Xiufan
Key Laboratory of Avian Bioproducts Development, Ministry of Agriculture and Rural Affairs, Yangzhou University, Yangzhou, 225009, China.
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, 225009, China.
Vet Res. 2025 Jun 8;56(1):111. doi: 10.1186/s13567-025-01534-8.
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.
自2021年以来，新型H10N3在中国已导致4例人类感染病例，其中最近一例发生在2024年12月，对公众健康构成了潜在威胁。我们之前的研究表明，几种禽H10N3毒株在小鼠中具有高致病性，并且可以在未经预先适应的情况下通过呼吸道飞沫在哺乳动物之间传播。通过分析基因组序列，我们发现这些H10N3病毒携带PB2-E627V突变，该突变在几种禽流感病毒（AIV）亚型中越来越常见；然而，其在哺乳动物适应中的机制仍不清楚。利用反向遗传学系统，我们研究了PB2-E627V在H10N3适应哺乳动物和家禽中的作用。我们的研究结果表明，PB2-E627V突变对于新型H10N3在小鼠中的高致病性及其在哺乳动物之间通过空气传播的能力至关重要。此外，我们发现PB2-627V在促进AIV适应哺乳动物方面的作用与PB2-627K相当。更重要的是，PB2-627V似乎同样适合在家禽中长期存在。因此，将PB2-627V用作评估AIV流行潜力的新型分子标记，对于预防未来可能的流感大流行具有重要意义。
