A systems approach to understanding human rhinovirus and influenza virus infection

Abstract

Human rhinovirus and influenza virus infections of the upper airway lead to colds and the flu and can trigger exacerbations of lower airway diseases including asthma and chronic obstructive pulmonary disease. Novel diagnostic and therapeutic targets are still needed to differentiate between the cold and the flu, since the clinical course of influenza can be severe while that of rhinovirus is usually more mild. In our investigation of influenza and rhinovirus infection of human respiratory epithelial cells, we used a systems approach to identify the temporally changing patterns of host gene expression from these viruses. After infection of human bronchial epithelial cells (BEAS-2B) with rhinovirus, influenza virus or co-infection with both viruses, we studied the time-course of host gene expression changes over three days. We modeled host responses to these viral infections with time and documented the qualitative and quantitative differences in innate immune activation and regulation.

Lung epithelial cells have virus-specific and shared gene expression responses to infection by diverse respiratory viruses

“…While rhinoviruses are known to down-regulate host gene expression by inhibiting transcription [30], upon RV infection we saw robust, early increases in host mRNA expression ( Fig 1C). This is in agreement with other transcriptome studies of major and minor serogroup rhinoviruses in human respiratory epithelial cells and experimental infections of humans [24,[31][32][33][34]. The plateau in gene expression changes in RV-infected cells at 24 h may be due to transcriptional inhibition later in infection, or the death of infected cells.…”

Despite Antagonism in vitro, Pseudomonas aeruginosa Enhances Staphylococcus aureus Colonization in a Murine Lung Infection Model

“…Explicitly, rhinoviruses increase S. aureus colonization by a mechanism involving the release of IL-6, IL-8, and the overexpression of ICAM-1 (Passariello et al, 2006). Moreover, rhinoviruses also upregulate integrin α 5 β 1 transcription (Kim et al, 2015). This integrin is one of the main pathways by which S. aureus can invade non-professional phagocytic cells (Josse et al, 2017).…”

Association of rhinovirus species with nasopharyngeal metabolome in bronchiolitis infants: A multicenter study

“…Lastly, we fit multivariable logistic regression models to examine the association (Tables S6 and S7 )and analysis using solo RV (without any coinfection) data (Tables S8 and S9 ) with RV species-level characterization, RV-A infection was associated with altered purine metabolism, which is involved in regulation of NF B-dependent cytokines and effector T-cell responses. 8 Additionally, RV-C infection was related to aberrant phosphoethanolamine and sphingolipid metabolism, which have molecular signaling functions in inflammation and immune responses. 9,10 The present study builds on these earlier reports and extends them by comprehensively profiling the airway metabolome and demonstrating their between-virus (and species) differences in a large cohort of infants with bronchiolitis.…”