ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Virus and Host
Human enterovirus D68 infection – The intricate dance of cells, genes, and invading bugs
Provisionally accepted- Faculty of Natural Sciences; Norwegian university of science and technology, Trondheim, Norway
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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 A Streptococcus and Streptococcus pneumoniae) 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 (MUC2, MUC5AC) and immune markers (TNFα and p38) compared to co-infections. In contrast, co-infections led to downregulation of sialic acid biosynthesis genes (CMAS, GNE, NANS), suggesting impaired receptor restoration and altered host-pathogen dynamics. These findings contribute to a deeper understanding of epithelial responses and highlight potential therapeutic targets.
Keywords: Human enterovirus D68, Respiratory epithelium, Streptococcus pneumoniae, Streptococcus pyogenes, respiratory infection, Co-infection
Received: 16 Jul 2025; Accepted: 27 Oct 2025.
Copyright: © 2025 Lillerovde Ørstenvik, Tveten and Cao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hanne Lillerovde Ørstenvik, hanne.l.orstenvik@ntnu.no
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