期刊
VETERINARY MICROBIOLOGY
卷 211, 期 -, 页码 129-134出版社
ELSEVIER
DOI: 10.1016/j.vetmic.2017.10.015
关键词
Avian influenza viruses; H9N2; Adaptation; Precision-cut lung slices; Well-differentiated epithelial cells
资金
- China Scholarship Council
- German FluResearchNet, a nationwide research network on zoonotic influenza - Ministry of Education and Research [01KI1006D]
- German Ministry of Education and Research 'FluResearchNet' [01KI1006F]
- Helmholtz-Association (Program Infection and Immunity)
We analyzed the adaptation of influenza viruses to growth in differentiated airway epithelial cells of a new host by passaging an avian H9N2 virus three times in porcine precision-cut lung slices (PCLS). Sequence analysis revealed four mutations: one each in the PB2 and NS1 proteins, and two in the HA protein. In this study, we characterized the PB2 mutation G685R by generating recombinant H9N2 viruses containing the PB2 single mutation alone or in combination with one of the HA mutations (A190V or T212I). When analyzed in porcine cells-a tracheal cell line (NPTr) or PCLS - the PB2-685 mutant did not provide a growth advantage and had no effect on the ciliary activity which is a virulence marker of swine influenza viruses. Pathogenicity for mice was also not increased by the single PB2 mutation. However, both double mutants (HA-190+PB2-685 and HA-212+PB2-685) showed significantly increased virulence in mice. Therefore, the mutations in the HA and PB2 proteins may confer early adaptation of an avian H9N2 virus to a mammalian host. In conclusion, we expect that a broader ensemble of mutations will be required to render an H9N2 virus virulent for pigs.
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