Human Enterovirus D68 infection – the intricate dance of cells, genes, and invading bugs

The respiratory tract is particularly vulnerable to infections from various pathogens, often leading to severe illnesses. Co-infections involving multiple pathogens are commonly observed in respiratory diseases, although their underlying mechanisms remain poorly understood. Lung epithelial cells play a crucial role in the body's defense and are primary targets for many pathogens, which exploit them for attachment and entry. This study investigates the molecular mechanism underlying co-infections of human enterovirus D68 (HEV-D68) and bacteria (Group <i>A Streptococcus</i> and <i>Streptococcus pneumoniae</i>) in lung epithelial cells. Cell viability and gene expression changes were assessed over a 24-hour period. The results revealed significant cytopathic effect and distinct gene expression patterns. HEV-D68 infection alone induced stronger upregulation of mucin genes (<i>MUC2</i>, <i>MUC5AC</i>) and immune markers (<i>TNFα</i> and <i>p38</i>) compared to co-infections. In contrast, co-infections led to downregulation of sialic acid biosynthesis genes (<i>CMAS</i>, <i>GNE</i>, <i>NANS</i>), suggesting impaired receptor restoration and altered host-pathogen dynamics. These findings contribute to a deeper understanding of epithelial responses and highlight potential therapeutic targets.