Increased expression of microRNA-155-5p by alveolar type II cells contributes to development of lethal ARDS in H1N1 influenza A virus-infected mice

Virology. 2020 Jun:545:40-52. doi: 10.1016/j.virol.2020.03.005. Epub 2020 Mar 23.

Abstract

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.

Keywords: Acute respiratory distress syndrome; Alveolar type II cell; Influenza A virus; Mouse; microRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Epithelial Cells / metabolism*
  • Alveolar Epithelial Cells / virology
  • Animals
  • Female
  • Humans
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Influenza, Human / genetics*
  • Influenza, Human / metabolism
  • Influenza, Human / mortality*
  • Influenza, Human / virology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Respiratory Distress Syndrome / genetics*
  • Respiratory Distress Syndrome / metabolism
  • Respiratory Distress Syndrome / mortality*
  • Respiratory Distress Syndrome / virology

Substances

  • MicroRNAs
  • Mirn155 microRNA, mouse