Pattern of gene expression in blood provides clues to etiology of respiratory infections

Scientists have shown that they can identify and characterize an individual's response to a respiratory viral infection by examining the pattern of gene expression in their blood.

The research, published by Cell Press online on August 6th in the journal Cell Host and Microbe, is the first step toward a blood test that may someday be used to decide who would benefit from an antiviral versus antibiotic treatment and possibly even determine prognosis after viral infection or therapeutic intervention.

Acute respiratory infections (ARI) are among the most common reasons for seeking medical treatment in the United States, and the impending threat of pandemic influenza is likely further increase these cases. There are many different types of ARI and some, such as influenza, can have a serious impact in infected individuals, especially those with prior pulmonary disease. Therefore, discrimination between infectious causes of an illness could have a profound impact on treatment decisions.

"Early detection and identification of the causal pathogen for upper respiratory infection can facilitate individual treatment decisions, as well as provide early data to forecast an epidemic/pandemic," offers senior study author, Dr. Geoffrey Ginsburg director of the Center for Genomic Medicine at the Duke Institute for Genome Sciences and Policy in Durham, North Carolina. "However, current rapid diagnostic methods are lacking in sensitivity."

Dr. Ginsburg and colleagues examined gene expression patterns in white blood cells of healthy human subjects who were challenged with one of three different viruses, the common cold, influenza and respiratory syncytial virus (RSV). White blood cells were chosen because they are integral to the host immune response. "While current infectious disease diagnostics rely on pathogen-based detection, the development of reproducible means for extracting RNA from whole blood, coupled with advanced statistical methods for analysis of complex datasets, now allows the possibility of classifying infections based on pathogen specific genetic signatures of disease," explains Dr. Ginsburg.

The researchers developed a blood mRNA expression signature that classified symptomatic human respiratory viral infection. This signature accurately identified influenza infection and could reliably distinguish between viral and bacterial infections as well as healthy individuals. "This work emphasizes the important concept that capturing the human host response to pathogen exposure may serve as the basis for both diagnostic testing as well as a window into the fundamental biology of infection," concludes Dr. Ginsburg.