Wilk Esther, Pandey Ashutosh K, Leist Sarah Rebecca, Hatesuer Bastian, Preusse Matthias, Pommerenke Claudia, Wang Junxi, Schughart Klaus
Department of Infection Genetics, Helmholtz Centre for Infection Research and University of Veterinary Medicine Hannover, Inhoffenstr. 7, 38124, Braunschweig, Germany.
Department of Genetics, Genomics and Informatics, Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, 855 Madison Avenue, Memphis, TN, 38163, USA.
BMC Genomics. 2015 Sep 2;16(1):655. doi: 10.1186/s12864-015-1867-8.
The host response to influenza A infections is strongly influenced by host genetic factors. Animal models of genetically diverse mouse strains are well suited to identify host genes involved in severe pathology, viral replication and immune responses. Here, we have utilized a dual RNAseq approach that allowed us to investigate both viral and host gene expression in the same individual mouse after H1N1 infection.
We performed a detailed expression analysis to identify (i) correlations between changes in expression of host and virus genes, (ii) host genes involved in viral replication, and (iii) genes showing differential expression between two mouse strains that strongly differ in resistance to influenza infections. These genes may be key players involved in regulating the differences in pathogenesis and host defense mechanisms after influenza A infections. Expression levels of influenza segments correlated well with the viral load and may thus be used as surrogates for conventional viral load measurements. Furthermore, we investigated the functional role of two genes, Reg3g and Irf7, in knock-out mice and found that deletion of the Irf7 gene renders the host highly susceptible to H1N1 infection.
Using RNAseq analysis we identified novel genes important for viral replication or the host defense. This study adds further important knowledge to host-pathogen-interactions and suggests additional candidates that are crucial for host susceptibility or survival during influenza A infections.
宿主对甲型流感感染的反应受到宿主遗传因素的强烈影响。具有遗传多样性的小鼠品系的动物模型非常适合用于鉴定参与严重病理、病毒复制和免疫反应的宿主基因。在这里，我们采用了一种双重RNA测序方法，使我们能够在H1N1感染后的同一只小鼠中研究病毒和宿主基因的表达。
我们进行了详细的表达分析，以确定（i）宿主和病毒基因表达变化之间的相关性，（ii）参与病毒复制的宿主基因，以及（iii）在对流感感染抵抗力差异很大的两种小鼠品系之间表现出差异表达的基因。这些基因可能是调节甲型流感感染后发病机制和宿主防御机制差异的关键因素。流感片段的表达水平与病毒载量密切相关，因此可用作传统病毒载量测量的替代指标。此外，我们在基因敲除小鼠中研究了Reg3g和Irf7这两个基因的功能作用，发现Irf7基因的缺失使宿主对H1N1感染高度敏感。
通过RNA测序分析，我们鉴定出了对病毒复制或宿主防御重要的新基因。这项研究为宿主-病原体相互作用增添了更多重要知识，并提出了在甲型流感感染期间对宿主易感性或生存至关重要的其他候选基因。
