Differential gene expression in the lungs of Syrian hamsters infected with Adenoviurs 14 or Adenovirus 14p1
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ABSTRACT: Adenovirus is a frequent cause of mild, usually self-limited infections in infants and young children. Severe infections occur in immunocompromised patients but are rarely observed in healthy, immunocompetent adults. However, there have been outbreaks around the world of infections with different adenoviral (Ad) serotypes that have resulted in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in some of those infected. Ad14p1, the predominant circulating strain of Ad14 worldwide is one such serotype. The explanations for the severity of illness caused by Ad14p1 infection in immunocompetent patients is unknown. Previously, we have shown that A549 cells infected with Ad14 repress macrophage pro-inflammatory responses whereas cells infected with Ad14p1 fail to repress macrophages and, instead, can increase pro-inflammatory responses. Micro-RNAs (miRNA) are small noncoding RNAs that regulate gene expression at the posttranscriptional level. Adenoviral infection has been shown to modulate host miRNA expression, and we hypothesized that differences in miRNA expression between Ad14 and Ad14p1 infected cells might impact pathogenesis. A549 cells were infected with either Ad14 or Ad14p1 and total RNA samples were collected at 6, 12, 24, 36 and 48 post infection for miRNA sequencing. Cluster analysis revealed that there were 3 temporal changes in miRNA expression profiles following infection. Differential expression analysis showed 8-23 differentially expressed miRNA between Ad14 and Ad14p1 from 6 to 36hpi. However, at 48hpi there were 98 differentially expressed miRNAs in Ad14p1 infected cells compared to those infected by Ad14. Pathway enrichment analysis showed that the differentially expressed miRNA might explain the increased pathogenesis of Ad14p1caused by strain-related loss of modulation of cytokine expression. Infection with Ad14p1 results in increased expression of pro-inflammatory genes in the lungs of Syrian hamsters than infection with Ad14. Overall, the data suggest a role for viral regulation of host miRNA expression in pathogenesis by regulating host inflammatory responses through the delivery of deregulated miRNAs by virally infected cell corpses to macrophages.
ORGANISM(S): Mesocricetus auratus
PROVIDER: GSE212833 | GEO | 2022/09/13
REPOSITORIES: GEO
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