Hao Xiaoli, Wang Jiongjiong, Hu Jiao, Lu Xiaolong, Gao Zhao, Liu Dong, Li Juan, Wang Xiaoquan, Gu Min, Hu Zenglei, Liu Xiaowen, Hu Shunlin, Xu Xiulong, Peng Daxin, Jiao Xinan, Liu Xiufan
Animal Infectious Disease Laboratory, School of Veterinary Medicine, Yangzhou University, Yangzhou, China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, China.
Front Microbiol. 2017 Oct 11;8:1978. doi: 10.3389/fmicb.2017.01978. eCollection 2017.
H9N2 avian influenza virus (AIV) of genotype S frequently donate internal genes to facilitate the generation of novel reassortants such as H7N9, H10N8, H5N2 and H5N6 AIVs, posing an enormous threat to both human health and poultry industry. However, the pathogenicity and transmission of reassortant H5 viruses with internal gene cassette of genotype S H9N2-origin in chickens and mice remain unknown. In this study, four H5 reassortants carrying the HA and NA genes from different clades of H5 viruses and the remaining internal genes from an H9N2 virus of the predominant genotype S were generated by reverse genetics. We found that all four H5 reassortant viruses showed attenuated virulence in both chickens and mice, thus leading to increased the mean death times compared to the corresponding parental viruses. Consistently, the polymerase activity and replication ability in mammalian and avian cells, and the cytokine responses in the lungs of chickens and mice were also decreased when compared to their respective parental viruses. Moreover, these reassortants transmitted from birds to birds by direct contact but not by an airborne route. Our data indicate that the internal genes as a whole cassette from genotype S H9N2 viruses play important roles in reducing the pathogenicity of the H5 recombinants in chickens and mice, and might contribute to the circulation in avian or mammalian hosts.
S基因型H9N2禽流感病毒（AIV）经常提供内部基因，以促进新型重配病毒的产生，如H7N9、H10N8、H5N2和H5N6 AIV，对人类健康和家禽业构成巨大威胁。然而，携带S基因型H9N2来源内部基因盒的H5重配病毒在鸡和小鼠中的致病性和传播性仍不清楚。在本研究中，通过反向遗传学产生了四种H5重配病毒，它们携带来自不同H5病毒分支的HA和NA基因，其余内部基因来自优势S基因型的H9N2病毒。我们发现，所有四种H5重配病毒在鸡和小鼠中均表现出毒力减弱，因此与相应的亲本病毒相比，平均死亡时间延长。一致地，与各自的亲本病毒相比，它们在哺乳动物和禽细胞中的聚合酶活性和复制能力以及鸡和小鼠肺部的细胞因子反应也降低。此外，这些重配病毒通过直接接触在鸟类之间传播，但不能通过空气传播途径传播。我们的数据表明，来自S基因型H9N2病毒的整个内部基因盒在降低H5重组病毒在鸡和小鼠中的致病性方面发挥着重要作用，并且可能有助于在禽类或哺乳动物宿主中传播。
