Zhao Xuejin, Tefsen Boris, Li Yan, Qi Jianxun, Lu Guangwen, Shi Yi, Yan Jinghua, Xiao Haixia, Gao George F
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, P. R. China.
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, P. R. China.
J Gen Virol. 2016 Aug;97(8):1797-1806. doi: 10.1099/jgv.0.000509. Epub 2016 May 23.
Influenza A viruses have the potential to cause pandemics due to the introduction of novel subtypes against which human hosts have little or no preexisting immunity. Such viruses may result from reassortment between human and animal influenza viruses. Recently, new influenza-like viruses were identified in bats, raising the concern for a new reservoir of potentially harmful influenza viruses that could form reassortants with categorized human influenza A viruses. However, until now, it has not been possible to generate a recombinant reassortant virus containing a single functional gene or domain from H17N10 that could propagate. Here, we demonstrate that a recombinant A/Puerto Rico/8/1934 (H1N1) virus with NS1 gene from H17N10 influenza-like virus can be successfully rescued. We used luciferase reporter assays and quantitative reverse transcriptase PCR to show that the NS1 protein from H17N10 inhibited Sendai-virus (SeV)-induced activation of IFN-β expression with an efficiency similar to NS1 from an H5N1 strain. Moreover, the crystal structure of the NS1 (H17N10) RNA-binding domain is also similar to that of other NS1s. These results demonstrate that H17N10 influenza-like virus indeed contains functional genes that are compatible with categorized influenza A viruses. Although the chance of this particular event occurring in nature seems negligible, further research is needed to address the possibility of the natural formation of reassortants.
甲型流感病毒有可能引发大流行，因为会出现新的病毒亚型，而人类宿主对这些亚型几乎没有或完全没有预先存在的免疫力。此类病毒可能是由人类和动物流感病毒之间的基因重配产生的。最近，在蝙蝠中发现了新的类流感病毒，这引发了人们对一个新的潜在有害流感病毒库的担忧，这些病毒可能会与已分类的甲型流感病毒形成重配病毒。然而，到目前为止，还无法产生一种含有来自H17N10的单个功能基因或结构域且能够传播的重组重配病毒。在此，我们证明，含有来自H17N10类流感病毒NS1基因的重组A/波多黎各/8/1934（H1N1）病毒能够成功拯救出来。我们使用荧光素酶报告基因检测和定量逆转录PCR表明，H17N10的NS1蛋白抑制仙台病毒（SeV）诱导的IFN-β表达激活的效率与H5N1毒株的NS1相似。此外，NS1（H17N10）RNA结合结构域的晶体结构也与其他NS1相似。这些结果表明，H17N10类流感病毒确实含有与已分类甲型流感病毒兼容且具有功能的基因。尽管这种特殊情况在自然界发生的可能性似乎微乎其微，但仍需要进一步研究来探讨重配病毒自然形成的可能性。
