Lan Riguo, Yang Jizhe, Li Jixiang, Li Han, Cao Xihao, Tao Mengyan, Chang Haoyu, Yu Haili, Tong Qi, Lu Lu, Liu Jinhua, Sun Honglei
National Key Laboratory of Veterinary Public Health and Safety, Key Laboratory for Prevention and Control of Avian Influenza and Other Major Poultry Diseases, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, China.
The Roslin Institute, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
J Virol. 2025 Sep 8:e0043025. doi: 10.1128/jvi.00430-25.
Swine influenza A virus (swIAV) is an important zoonotic pathogen with the potential to cause human influenza pandemics. Swine are considered "mixing vessels" for generating novel reassortant influenza A viruses. In 2009, a swine-origin reassortant virus (2009 pandemic H1N1, pdm/09 H1N1) spilled over to humans, causing a global influenza pandemic. This virus soon spread back into swine herds and reassorted with the circulating swIAVs. We previously reported that the genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bore pdm/09- and triple reassortant (TR)-derived internal genes, had been predominant in swine populations of China since 2016, posing a threat to both the swine industry and public health. Here, our ongoing surveillance confirmed that G4 EA H1N1 viruses remained the predominant swIAVs in China from 2019 to 2023 and had reassorted with the co-circulating swIAVs, such as the H3N2 virus, to generate novel reassortant EA H1N2 viruses. Genetic analyses revealed that the pdm/09-derived internal genes of G4 EA H1N1 viruses originated from reassortments between pdm/09 H1N1 and EA H1N1 viruses in 2009-2010 and underwent independent and continuous evolution in the swine host, exhibiting higher evolutionary rates than those of the pdm/09 H1N1 virus circulating in humans. The accelerated evolution of internal genes enhanced the polymerase activity of G4 EA H1N1 viruses in mammalian cells, resulting in increased viral replication and pathogenicity in mice. This study provides evidence for swine in promoting the genetic evolution of influenza A virus and highlights the need for increased attention to novel reassortant viruses in swine.IMPORTANCEThe emergence of pdm/09 H1N1 virus highlights the role of swine influenza A viruses (swIAVs) in generating novel influenza viruses with pandemic potential. Since 2009, the pdm/09 H1N1 virus has been frequently transmitted to swine and reassorted with the circulating swIAVs, generating many new reassortant viruses bearing pdm/09-derived genes globally. The G4 EA H1N1 viruses, which bore pdm/09-derived internal genes and acquired increased human infectivity, remained the predominant swIAVs in China from 2019 to 2023 and reassorted with the co-circulating swIAVs to generate novel subtype viruses. The internal genes of G4 EA H1N1 viruses originated from the human pdm/09 H1N1 viruses during 2009-2010 and exhibited higher evolutionary rates and greater genetic diversity than those in the human host. This has contributed to increased viral adaptation and pathogenicity in mammals. Therefore, sustained surveillance and immunization efforts are essential to control emerging reassortant swIAVs and protect public health.
甲型猪流感病毒（swIAV）是一种重要的人畜共患病原体，有可能引发人类流感大流行。猪被认为是产生新型重配甲型流感病毒的“混合容器”。2009年，一种猪源重配病毒（2009年大流行H1N1，pdm/09 H1N1）传播给人类，引发了全球流感大流行。这种病毒很快又传回猪群，并与正在传播的swIAV重配。我们之前报道，基因型4（G4）重配的欧亚禽源样（EA）H1N1病毒携带pdm/09和三重重配（TR）衍生的内部基因，自2016年以来在中国猪群中占主导地位，对养猪业和公共卫生都构成威胁。在此，我们持续的监测证实，G4 EA H1N1病毒在2019年至2023年期间仍是中国主要的swIAV，并与共同传播的swIAV如H3N2病毒重配，产生了新型重配EA H1N2病毒。基因分析显示，G4 EA H1N1病毒的pdm/09衍生内部基因起源于2009 - 2010年pdm/09 H1N1和EA H1N1病毒之间的重配，并在猪宿主中经历了独立且持续的进化，其进化速率高于在人类中传播的pdm/09 H1N1病毒。内部基因的加速进化增强了G4 EA H1N1病毒在哺乳动物细胞中的聚合酶活性，导致病毒在小鼠中的复制增加和致病性增强。本研究为猪在促进甲型流感病毒基因进化中的作用提供了证据，并强调需要更多关注猪中出现的新型重配病毒。
重要性
pdm/09 H1N1病毒的出现凸显了甲型猪流感病毒（swIAV）在产生具有大流行潜力的新型流感病毒中的作用。自2009年以来，pdm/09 H1N1病毒频繁传播到猪群并与正在传播的swIAV重配，在全球产生了许多携带pdm/09衍生基因的新型重配病毒。G4 EA H1N1病毒携带pdm/09衍生的内部基因且人类感染性增加，在2019年至2023年期间仍是中国主要的swIAV，并与共同传播的swIAV重配产生新型亚型病毒。G4 EA H1N1病毒的内部基因在2009 - 2010年期间起源于人类pdm/09 H1N1病毒，与人类宿主相比表现出更高的进化速率和更大的遗传多样性。这导致了病毒在哺乳动物中的适应性和致病性增加。因此，持续的监测和免疫工作对于控制新出现的重配swIAV和保护公共卫生至关重要。
