Gene Expression Signatures Diagnose Influenza and Other Symptomatic Respiratory Viral Infections in Humans

Abstract

Summary Acute respiratory infections (ARI) are a common reason for seeking medical attention and the threat of pandemic influenza will likely add to these numbers. Using human viral challenge studies with live rhinovirus, respiratory syncytial virus, and influenza A, we developed peripheral blood gene expression signatures that distinguish individuals with symptomatic ARI from uninfected individuals with > 95% accuracy. We validated this “acute respiratory viral” signature - encompassing genes with a known role in host defense against viral infections - across each viral challenge. We also validated the signature in an independently acquired dataset for influenza A and classified infected individuals from healthy controls with 100% accuracy. In the same dataset, we could also distinguish viral from bacterial ARIs (93% accuracy). These results demonstrate that ARIs induce changes in human peripheral blood gene expression that can be used to diagnose a viral etiology of respiratory infection and triage symptomatic individuals.

Gene expression profiles in febrile children with defined viral and bacterial infection

“…It is also possible that differences among groups would be sharpened by extracting RNA from specific leukocyte populations. Despite these considerations, the identity of many virus-specific classifier genes was similar to a previous study on respiratory viral infections (11). Finally, as is true for many gene expression microarray studies, our study was challenged by dimensionality, because the number of parameters measured vastly exceeded the number of study subjects (15).…”

“…Other studies have attempted to use host transcriptional signatures to distinguish viral from bacterial infection (6,11). In the present study, we used several approaches to developing a panel of probes that could make this important distinction.…”

“…In addition, specific blood transcriptional signatures were defined in adult volunteers challenged with specific respiratory viruses (11). Analysis of host transcriptional profiles has also been applied to the diagnosis of inflammatory and hematological diseases (12)(13)(14)(15), including the identification of potential biomarkers for specific disease entities (5).…”

Controlled human infection with RSV: The opportunities of experimental challenge

“…The first published study using this virus in humans was by Zaas et al in 2009 [29]. The objective was to identify a peripheral blood mRNA signature to diagnose acute respiratory viral infection.…”

Cancer trial errors revealed

“…McKinney told Nature that he is troubled by one study co-authored by Geoffrey Ginsburg, a physician at the ISGP. In the study 5 , approved by Duke's Institutional Review Board and review boards at four further institutions, 57 people were infected with cold or influenza viruses. Gene-expression data were then obtained to see whether it was possible to retrospectively 'predict' which virus they had been infected with -information that could aid the prompt detection of a pandemic.…”