Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
Virology. 2011 Dec 20;421(2):105-13. doi: 10.1016/j.virol.2011.09.011. Epub 2011 Oct 13.
Infections with highly pathogenic H5N1 avian (HPAI) and 1918 pandemic H1N1 influenza viruses cause uncontrolled local and systemic inflammation. The mechanism for this response is poorly understood, despite its importance as a determinant of virulence. Therefore we profiled cellular microRNAs of lung tissue from cynomolgus macaques (Macaca fascicularis) infected with a HPAI and a less pathogenic 1918 H1N1 reassortant virus to understand microRNA contribution to host response. We identified 23 microRNAs associated with the extreme virulence of HPAI, with expression patterns inversely correlated with that of predicted gene targets. Pathway analyses confirmed that these targets were associated with aberrant and uncontrolled inflammatory responses and increased cell death. Importantly, similar microRNAs were associated with lethal 1918 pandemic virus infections in mice. This study suggests that virulence of highly pathogenic influenza viruses may be mediated in part by cellular microRNA through dysregulation of genes critical to the inflammatory process.
高致病性 H5N1 禽流感（HPAI）和 1918 年大流行 H1N1 流感病毒感染会导致无法控制的局部和全身炎症。尽管这种反应的重要性是决定病毒毒力的因素之一，但人们对其机制仍了解甚少。因此，我们对感染高致病性 HPAI 和致病性较低的 1918 年 H1N1 重配病毒的食蟹猴（Macaca fascicularis）肺部组织中的细胞 microRNA 进行了分析，以了解 microRNA 对宿主反应的贡献。我们鉴定了与 HPAI 极强毒力相关的 23 种 microRNA，其表达模式与预测的基因靶标相反。途径分析证实，这些靶标与异常和不受控制的炎症反应以及细胞死亡增加有关。重要的是，在小鼠中，类似的 microRNA 与致命的 1918 年大流行病毒感染有关。本研究表明，高致病性流感病毒的毒力可能部分通过细胞 microRNA 通过对炎症过程关键基因的失调来介导。
