Mutation May Explain Why Some Get More Severe RSV Disease

RSV infection may cause mild, cold-like symptoms, or more serious symptoms, leading to hospitalization and even death.

A mutation in the gene of a white blood cell protein contributes to the severity of respiratory syncytial virus (RSV) infection, according to a paper published in EBioMedicine by researchers at NIEHS and their collaborators. RSV contributes to bronchiolitis, pneumonia, asthma and respiratory failure. It is also the leading cause of respiratory illness in infants, immunocompromised adults and the elderly.

The team used genome-wide association studies in mice to identify candidate genes involved in RSV severity. The most promising gene, macrophage receptor with collagenous structure (MARCO), produces a protein that allows a particular type of white blood cell to fight infection. The finding was surprising because MARCO had not previously been associated with RSV.

Mice with the MARCO gene knocked out experienced more severe symptoms from exposure to RSV, compared to wild-type mice. And effects in humans are strikingly similar. In two independent populations of children, infants born with a mutated MARCO gene exhibited more severe RSV symptoms than those with the wild-type gene.

“MARCO is an immune system gene that helps clear inflammation,” said Dr. Steven Kleeberger, lead researcher on the study. “If the gene is mutated, it can’t resolve the inflammation, so cells and mucus remain in the lung, blocking the airway.”

Using information learned from mouse and human studies, the team hopes to develop a diagnostic tool to identify infants subject to severe RSV disease before they get sick. There is no vaccine for RSV and some of its health effects are irreversible, so preventing even a small number of RSV-induced asthma or pneumonia cases could have a huge impact.