Dynamic changes in host gene expression associated with H5N8 avian influenza virus infection in mice.
Dynamic changes in host gene expression associated with H5N8 avian influenza virus infection in mice.
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小鼠中与H5N8禽流感病毒感染相关的宿主基因表达的动态变化。
DOI：
10.1038/srep16512
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发表时间：
2015-11-18
影响因子：
4.6
通讯作者：
Shin OS
中科院分区：
文献类型：
--
作者：
Park SJ;Kumar M;Kwon HI;Seong RK;Han K;Song JM;Kim CJ;Choi YK;Shin OS
新发现的高致病性禽流感（HPAI）A（H5 N8）病毒在全球范围内爆发。先前的研究表明，与H5 N1致病性相比，H5 N8在小鼠中的致病性相对中等。然而，禽流感致病性的详细机制仍然没有确定。我们使用高通量RNA-seq方法分析了感染A/MD/Korea/W 452/2014（H5 N8）和A/EM/Korea/W149/2006（H5 N1）病毒的小鼠肺部的宿主和病原体转录组。在感染后1天（dpi）的病毒转录物的序列数和宿主免疫相关基因的表达水平在H5 N8感染的小鼠中高于H5 N1感染的小鼠。病毒转录物的双重测序显示，与在感染后1天的观察结果相反，在感染后3天和7天测序的H5 N1基因数量高于H5 N8基因，这与体内感染肺中观察到的较高病毒滴度和毒力一致。免疫途径分析显示，在3和7 dpi时，H5 N1比H5 N8感染驱动的死亡受体信号转导的上调更显著。免疫应答相关基因的早期诱导可能在H5 N8感染的小鼠中引起保护作用，这与体内中度致病性相关。总的来说，我们的数据提供了新的见解的差异致病性禽流感病毒的潜在机制。
Emerging outbreaks of newly found, highly pathogenic avian influenza (HPAI) A(H5N8) viruses have been reported globally. Previous studies have indicated that H5N8 pathogenicity in mice is relatively moderate compared with H5N1 pathogenicity. However, detailed mechanisms underlying avian influenza pathogenicity are still undetermined. We used a high-throughput RNA-seq method to analyse host and pathogen transcriptomes in the lungs of mice infected with A/MD/Korea/W452/2014 (H5N8) and A/EM/Korea/W149/2006 (H5N1) viruses. Sequenced numbers of viral transcripts and expression levels of host immune-related genes at 1 day post infection (dpi) were higher in H5N8-infected than H5N1-infected mice. Dual sequencing of viral transcripts revealed that in contrast to the observations at 1 dpi, higher number of H5N1 genes than H5N8 genes was sequenced at 3 and 7 dpi, which is consistent with higher viral titres and virulence observed in infected lungs in vivo. Ingenuity pathway analysis revealed a more significant upregulation of death receptor signalling, driven by H5N1 than with H5N8 infection at 3 and 7 dpi. Early induction of immune response-related genes may elicit protection in H5N8-infected mice, which correlates with moderate pathogenicity in vivo. Collectively, our data provide new insight into the underlying mechanisms of the differential pathogenicity of avian influenza viruses.