Abstract The unprecedented spread of H5N8- and H9N2-subtype avian influenza virus (AIV) in birds across Asia, Europe, Africa, and North America poses a serious public health threat with a permanent risk of reassortment and the possible emergence of novel virus variants with high virulence in mammals. To gain information on this risk, we studied the potential for reassortment between two contemporary H9N2 and H5N8 viruses. While the replacement of the PB2, PA, and NS genes of highly pathogenic H5N8 by homologous segments from H9N2 produced infectious H5N8 progeny, PB1 and NP of H9N2 were not able to replace the respective segments from H5N8 due to residues outside the packaging region. Furthermore, exchange of the PB2, PA, and NS segments of H5N8 by those of H9N2 increased replication, polymerase activity and interferon antagonism of the H5N8 reassortants in human cells. Notably, H5N8 reassortants carrying the H9N2-subtype PB2 segment and to lesser extent the PA or NS segments showed remarkably increased virulence in mice as indicated by rapid onset of mortality, reduced mean time to death and increased body weight loss. Simultaneously, we observed that in chickens the H5N8 reassortants, particularly with the H9N2 NS segment, demonstrated significantly reduced transmission to co-housed chickens. Together, while the limited capacity for reassortment between co-circulating H9N2 and H5N8 viruses and the reduced bird-to-bird transmission of possible H5N8 reassortants in chickens may limit the evolution of such reassortant viruses, they show a higher replication potential in human cells and increased virulence in mammals.

中文翻译：

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鸡的遗传不相容性和传播减少可能会限制 H9N2 和泛动物 H5N8 进化枝之间的重配进化 2.3.4.4 对哺乳动物显示高毒力的禽流感病毒

摘要 H5N8 和 H9N2 亚型禽流感病毒 (AIV) 在亚洲、欧洲、非洲和北美洲的鸟类中空前传播，构成了严重的公共卫生威胁，具有重新组合的永久性风险，并且可能出现具有以下特征的新型病毒变种。在哺乳动物中具有高毒力。为了获得有关这种风险的信息，我们研究了两种当代 H9N2 和 H5N8 病毒之间重新组合的可能性。虽然用来自 H9N2 的同源片段替换高致病性 H5N8 的 PB2、PA 和 NS 基因产生了感染性 H5N8 后代，但 H9N2 的 PB1 和 NP 无法替换来自 H5N8 的相应片段，原因是包装区域外的残留物。此外，H5N8 的 PB2、PA 和 NS 片段被 H9N2 的片段交换增加了复制，人类细胞中 H5N8 重配体的聚合酶活性和干扰素拮抗作用。值得注意的是，携带 H9N2 亚型 PB2 片段和在较小程度上携带 PA 或 NS 片段的 H5N8 重配子在小鼠中显示出显着增加的毒力，如死亡率迅速发生、平均死亡时间缩短和体重减轻增加所表明的。同时，我们观察到，在鸡中，H5N8 重配体，尤其是 H9N2 NS 片段，表现出显着降低了对共同饲养鸡的传播。总之，虽然共同循环的 H9N2 和 H5N8 病毒之间的重排能力有限，以及鸡中可能的 H5N8 重排病毒在鸟与鸟之间传播的减少可能会限制此类重排病毒的进化，但它们在人类细胞中显示出更高的复制潜力，哺乳动物的毒力增加。