Alveolar type II (ATII) cells are essential to lung function and a primary site of influenza A virus (IAV) replication. Effects of IAV infection on ATII cell microRNA (miR) expression have not been comprehensively investigated. Infection of C57BL/6 mice with 10,000 or 100 pfu/mouse of IAV A/WSN/33 (H1N1) significantly altered expression of 73 out of 1908 mature murine miRs in ATII cells at 2 days post-infection (d.p.i.) and 253 miRs at 6 d.p.i. miR-155-5p (miR-155) showed the greatest increase in expression within ATII cells at both timepoints and the magnitude of this increase correlated with inoculum size and pulmonary edema severity. Influenza-induced lung injury was attenuated in C57BL/6-congenic miR-155-knockout mice without affecting viral replication. Attenuation of lung injury was dependent on deletion of miR-155 from stromal cells and was recapitulated in ATII cell-specific miR-155-knockout mice. These data suggest that ATII cell miR-155 is a potential therapeutic target for IAV-induced ARDS.

中文翻译：

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肺泡 II 型细胞增加 microRNA-155-5p 的表达有助于在 H1N1 甲型流感病毒感染的小鼠中发生致命的 ARDS。

肺泡 II 型 (ATII) 细胞对肺功能和甲型流感病毒 (IAV) 复制的主要部位至关重要。尚未全面研究 IAV 感染对 ATII 细胞 microRNA (miR) 表达的影响。用 10,000 或 100 pfu/小鼠 IAV A/WSN/33 (H1N1) 感染 C57BL/6 小鼠在感染后 2 天 (dpi) 显着改变 ATII 细胞中 1908 个成熟鼠 miRs 中的 73 个和 253 个 miRs 的表达6 dpi miR-155-5p (miR-155) 在两个时间点均显示 ATII 细胞内表达的最大增加，并且这种增加的幅度与接种量和肺水肿严重程度相关。流感诱导的肺损伤在 C57BL/6 同类 miR-155 敲除小鼠中减弱，而不影响病毒复制。肺损伤的减轻依赖于基质细胞中 miR-155 的缺失，并在 ATII 细胞特异性 miR-155 敲除小鼠中得到概括。这些数据表明 ATII 细胞 miR-155 是 IAV 诱导的 ARDS 的潜在治疗靶点。