Studies Identify Biomarker for Infant Lung Infection

A viral protein that creates respiratory syncytial virus (RSV), the most common cause for hospitalization in children under 12 months old, has been identified, according to research published in the Journal of Clinical Investigation.

Researchers from the University of North Carolina School of Medicine compared the infection abilities of RSV and parainfluenza virus (PIV3) in cell culture models of human epithelial cells. Although this comparison did not yield any fruitful results, the researchers noted the RSV-infected cells differed in appearance from their PIV3-infected counterparts.

While the PIV3-infected cells remained unchanged in shape, the RSV-infected cells puffed out, which caused the cells to accumulate in the lumen of the airway. Thus, the research team hypothesized the difference resulted from the types of genes that RSV expressed.

“We’ve now shown that RSV has an increased ability to cause airway obstruction because, during an RSV infection, the virus expresses a specific RSV-encoded non-structural protein (NS2) in epithelial cells, causing the cells to shed from the airway lining and into the airway lumen,” senior study author Raymond Pickles, PhD, said in a statement. “This leads to obstruction of airflow in the small airways and overwhelming inflammation.”

By examining the types of genes that RSV expresses, the researchers discovered the NS2 gene was responsible for the cells’ puffing and shedding from lining. When scientists engineered PIV3 cells to express RSV NS2, the infected cells puffed up similarly to the RSV-infected cells.

The investigators tested those reengineered cells in animal models and found epithelial cells lining the airways were shed into the airway lumen at such a rate that it caused excessive inflammation.

Pickles said this mirrored what occurred in human infants who died due to RSV. “I’m convinced that the RSV NS2 gene is a major driver for the well-recognized increased ability of RSV to cause lung disease, especially in the extremely narrow small airways of human infants,” he said.

The researchers said their next step is to find candidate molecular biomarkers that would indicate whether the epithelial cells in small airways are expressing the RSV NS2 protein, which Pickles noted he already found. The driving force behind the study is to more quickly identify children at risk for severe lung disease and get them into treatment protocols sooner.

Pickles said he plans to suppress the ability of NS2 to puff up epithelial cells. While this would not stop the infection or other symptoms of RSV, it could thwart the ability of the virus to spread to small airways that would be obstructed during the puffing and shedding processes.