UW-Madison: UW scientists find key link in cold-virus picture

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MADISON—Researchers at University of Wisconsin School of Medicine and Public Health (SMPH) have made a key discovery about a cold-causing virus that is strongly associated with severe asthma attacks. The findings point to a new target for reducing both colds and asthma attacks linked to the virus.

The research team identified a cellular receptor for rhinovirus C (RV-C), a kind of ‘docking station’ where the virus attaches to the cell and starts to multiply. A variant in the gene for this receptor had been linked to asthma in past genetic studies, but the potential role of the receptor, called CDHR3, in asthma was previously unknown.

The new findings, published April 6 in the Proceedings of the National Academy of Sciences (PNAS), help clarify the function of CDHR3 and may lead to the development of prevention and treatment strategies against RV-C-induced colds and asthma attacks.

“This virus had been hard to study because none of the standard cell lines in the laboratory would permit growth of RV-C because the virus bound to an unknown receptor on the surface of cells,” said Dr. James Gern, professor in the departments of pediatrics and medicine at UW and principal investigator of the study. “But our research describes the protein (CDHR3) that enables RV-C viruses to bind to cells, enter them and ultimately start the replication process.”

Like all viruses, RV-C uses the molecular machinery of host cells to replicate and become infectious. The researchers identified CDHR3 as a potential candidate by analyzing cells that either were or were not susceptible to RV-C infection. When engineered to produce CDHR3, cells that normally were not susceptible to rhinovirus C could bind the virus and support its replication.

Notably, cells bearing a specific CDHR3 gene variant showed greatly enhanced RV-C binding and produced more of the virus than cells with normal CDHR3. In previous genetic studies, this variant had been linked to a greater risk of wheezing illnesses and asthma hospitalizations during childhood. The new findings suggest that this gene variant could be a risk factor for childhood wheezing illnesses caused by rhinovirus C, which in turn may increase the risk of developing asthma. In the future, development of drugs that block CDHR3 potentially could help prevent and treat illnesses caused by rhinovirus C.

Together with rhinoviruses A and B, RV-C is responsible for millions of illnesses yearly at an estimated annual cost of more than $40 billion in the United States alone.

Yury Bochkov is the lead author on the study, and members of the SMPH research team that conducted the research include, Kelly Watters, Shamaila Ashraf, Theodor Griggs, Mark Devries, Daniel Jackson, and Ann Palmenberg. The study was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.