By: JOE MONTGOMERY
KSU College of Veterinary Medicine
Respiratory syncytial virus, more commonly known as RSV, sends thousands of young children to the hospital each year, and treatment options remain limited.
New research from the College of Veterinary Medicine at Kansas State University is helping address and mitigate the effects of the troublesome virus.
Pankaj Baral, associate professor of immunology in the Department of Diagnostic Medicine/Pathobiology, and doctoral student Sandeep Adhikari recently published a paper in the journal Nature Communications detailing the role of the beta-adrenergic signaling pathway in RSV infections.
Using an animal model of RSV infection, the researchers tested how a drug that targets a common airway adrenergic receptor affects infection and inflammation.
How the nervous system helps young lungs fight RSV
The sympathetic nervous system is a critical aspect of the body-brain connection and organismic defense. These neurons are involved in the "fight-or-flight" response and secrete neurotransmitter norepinephrine, which binds to beta-adrenergic receptors in smooth muscle and immune cells.
“The role of the nervous system in antiviral immunity during early-life infections is not well understood,” Baral said. “Our study produces insight into the role of sympathetic neurons and beta-2 adrenergic receptor signaling in promoting antiviral defense mechanisms during neonatal infection with RSV, a respiratory virus that causes mild to severe infections in young children and animals.”
The virus is the most common cause of infection and other acute respiratory disorders in children under 5 years of age, Baral said, although RSV can occasionally be problematic for older people and animals.
RSV infections are characterized by lung inflammation, viral expansion and destruction of airway barriers, so it’s critically important to find ways to inhibit infections from occurring.
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“It is unknown whether beta-adrenergic signaling can regulate antiviral immunity during early-life infections,” Baral said. “In our research, we find that stimulation of adrenergic signaling via Beta-2-adrenergic agonist increases viral clearance and anti-inflammatory responses, two major aspects of antiviral immunity.”
Beta-2-adrenergic agonists, also known as beta agonists, are widely used Food and Drug Administration-approved drugs for bronchodilation in patients with asthma and chronic obstructive pulmonary disease.
Despite being a commonly used drug, its immune regulatory and antiviral potential in viral infection is less understood. While more research is needed before the findings can influence patient care, Baral's work opens the door to new ways of protecting infants during their most vulnerable months.
“Our study generates a proof-of-concept regarding the potential therapeutic role of beta-2 agonist for improving disease morbidity and viral clearance during RSV infections,” Adhikari said. “Our findings are significant as current monoclonal antibody therapies and maternal vaccines do not provide long-term protection against RSV.”
“It’s a significant recognition of our graduate program that a graduate student-led study got published in one of the most prestigious and high-impact journals,” said T.G. Nagaraja, program director of the doctoral pathobiology program in the College of Veterinary Medicine.
This newly published work was supported by funding from the American Lung Association, the National Institutes of Health, and the American Heart Association to the Baral Laboratory.
The research article is titled, “β2-adrenergic signaling controls neonatal respiratory syncytial virus infection by promoting viral clearance and airway protection,” in the Dec. 18. issue of Nature Communications.