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

Parker S Woods1, Lauren M Doolittle1, Lucia E Rosas1

  • 1Department of Veterinary Biosciences, College of Veterinary Medicine, Columbus, OH, USA.

Virology
|April 21, 2020
PubMed

Insights

Influenza A virus infection alters microRNA (miR) expression in lung cells. Targeting miR-155 in alveolar type II cells may reduce influenza-induced lung injury and acute respiratory distress syndrome (ARDS).

Area of Science:

  • Pulmonology
  • Virology
  • Molecular Biology

Background:

  • Alveolar type II (ATII) cells are crucial for lung function and are a key replication site for influenza A virus (IAV).
  • The impact of IAV infection on microRNA (miR) expression in ATII cells remains incompletely understood.

Purpose of the Study:

  • To investigate the comprehensive effects of IAV infection on ATII cell microRNA expression.
  • To determine the role of miR-155 in IAV-induced lung injury and its potential as a therapeutic target.

Main Methods:

  • C57BL/6 mice were infected with IAV A/WSN/33 (H1N1) at different doses.
  • MicroRNA expression profiling was performed on ATII cells at 2 and 6 days post-infection.
  • miR-155-knockout mice (both congenic and ATII cell-specific) were used to assess the role of miR-155 in lung injury.

Main Results:

  • IAV infection significantly altered the expression of numerous miRs in ATII cells.
  • miR-155-5p (miR-155) exhibited the most substantial increase in expression, correlating with viral inoculum size and lung edema severity.
  • Lung injury was reduced in miR-155-knockout mice, indicating miR-155's critical role in influenza-induced pathogenesis.

Conclusions:

  • ATII cell miR-155 expression is significantly upregulated following IAV infection.
  • miR-155 contributes to influenza-induced lung injury, independent of viral replication.
  • Targeting ATII cell miR-155 presents a potential therapeutic strategy for managing IAV-induced acute respiratory distress syndrome (ARDS).