Yang Jianmei, Lee Jinhwa, Ma Jingjiao, Lang Yuekun, Nietfeld Jerome, Li Yuhao, Duff Michael, Li Yonghai, Yang Yuju, Liu Haixia, Zhou Bin, Wentworth David E, Richt Juergen A, Li Zejun, Ma Wenjun
Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
Innovation Team for Pathogen Ecology Research on Animal Influenza Virus, Department of Avian Infectious Disease, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, PR China.
J Gen Virol. 2017 Apr;98(4):577-584. doi: 10.1099/jgv.0.000715. Epub 2017 Apr 20.
In our previous studies, the reassortant virus containing only the PR8 H1N1 matrix (M) gene in the background of the modified bat influenza Bat09 : mH1mN1 virus could be generated. However, whether M genes from other origins can be rescued in the background of the Bat09 : mH1mN1 virus and whether the resulting novel reassortant virus is virulent remain unknown. Herein, two reassortant viruses were generated in the background of the Bat09 : mH1mN1 virus containing either a North American or a Eurasian swine influenza virus M gene. These two reassortant viruses and the reassortant virus with PR8 M as well as the control Bat09 : mH1mN1 virus replicated efficiently in cultured cells, while the reassortant virus with PR8 M grew to a higher titre than the other three viruses in tested cells. Mouse studies showed that reassortant viruses with either North American or Eurasian swine influenza virus M gene did not enhance virulence, whereas the reassortant virus with PR8 M gene displayed higher pathogenicity when compared to the Bat09 : mH1mN1 virus. This is most likely due to the fact that the PR8 H1N1 virus is a mouse-adapted virus. Furthermore, reassortment potential between the Bat09 : mH1mN1 virus and an H3N2 swine influenza virus (A/swine/Texas/4199-2/1998) was investigated using co-infection of Madin-Darby canine kidney cells, but no reassortant viruses were detected. Taken together, our results indicate that the modified bat influenza virus is most likely incapable of reassortment with influenza A viruses with in vitro co-infection experiments, although reassortant viruses with different M genes can be generated by reverse genetics.
在我们之前的研究中，可以产生在修饰的蝙蝠流感病毒Bat09 : mH1mN1背景下仅含有PR8 H1N1基质（M）基因的重配病毒。然而，来自其他来源的M基因是否能在Bat09 : mH1mN1病毒背景下拯救出来，以及由此产生的新型重配病毒是否具有毒性仍然未知。在此，在Bat09 : mH1mN1病毒背景下产生了两种重配病毒，分别含有北美或欧亚猪流感病毒的M基因。这两种重配病毒、含有PR8 M基因的重配病毒以及对照Bat09 : mH1mN1病毒在培养细胞中均能高效复制，而含有PR8 M基因的重配病毒在受试细胞中的滴度高于其他三种病毒。小鼠研究表明，含有北美或欧亚猪流感病毒M基因的重配病毒不会增强毒力，而与Bat09 : mH1mN1病毒相比，含有PR8 M基因的重配病毒表现出更高的致病性。这很可能是因为PR8 H1N1病毒是一种适应小鼠的病毒。此外，通过共感染Madin-Darby犬肾细胞研究了Bat09 : mH1mN1病毒与H3N2猪流感病毒（A/猪/德克萨斯/4199-2/1998）之间的重配潜力，但未检测到重配病毒。综上所述，我们的结果表明，尽管通过反向遗传学可以产生含有不同M基因的重配病毒，但在体外共感染实验中，修饰的蝙蝠流感病毒很可能无法与甲型流感病毒发生重配。
