Host genetic background strongly affects pulmonary miRNA expression before and during evolution of influenza A virus infection

ABSTRACT: Background: The role of host encoded microRNAs in genetically determined host susceptibility to influenza A virus (IAV) infection has not been explored. We therefore compared changes in pulmonary miRNA expression during IAV infection in two inbred mouse strains with differential susceptibility to IAV infection. Results: miRNA expression profiles were determined in lungs of the more susceptible mouse strain DBA/2J and the less susceptible strain C57BL/6J within 120 hours post infection (hpi) with IAV (H1N1) PR8. Even the miRNomes of uninfected lungs differed substantially between the two strains. After a period of relative quiescence, major miRNome reprogramming was detected in both strains by 48 hpi and increased through 120 hpi. Distinct groups of miRNAs regulated by IAV infection could be defined: (1) miRNAs (n= 39) whose expression correlated with HA mRNA expression and represented the general response to IAV infection independent of host genetic background; (2) miRNAs (n=20) whose expression correlated with HA mRNA expression but differed between the two strains; and (3) remarkably, miRNAs (n=8) whose abundance even in uninfected lungs differentiated nearly perfectly (area under the ROC curve >0.99) between the two strains throughout the time course. Higher abundance of miRNAs with anti-apoptotic functions and lower abundance of miRNAs regulating the PI3K-Akt pathway were associated with the more susceptible DBA/2J strain. Conclusions: These results suggest that differences in host miRNA abundance before and during IAV infection are in part determined genetically and contribute to susceptibility to IAV infection in this experimental mouse model, and likely in humans.

ORGANISM(S): Mus musculus

PROVIDER: GSE89064 | GEO | 2017/06/12

SECONDARY ACCESSION(S): PRJNA350206

REPOSITORIES: GEO