The common cold is a regular nuisance for most of us. The average healthy adult has two to three colds per year. Cold viruses usually cause mild symptoms—such as a sore throat, runny nose, and cough—and are quickly removed by the immune system. But for some people, particularly children and older adults with underlying health problems, cold viruses can lead to more severe health problems.
Human rhinovirus (HRV) is the main cause of the common cold, making up over half of the cases. Despite the prevalence of colds, the immune response to these viruses isn’t well understood. A better understanding could help researchers develop effective therapies against HRV and other cold viruses.
A case study by researchers at NIH’s National Institute of Allergy and Infectious Diseases (NIAID) revealed an important mechanism by which the immune system responds to HRV. The case involved a child who, several weeks after birth, started getting life-threatening respiratory infections. Her doctors at National Jewish Health and NIH suspected she might have a genetic abnormality affecting her immune system. Led by NIAID’s Dr. Helen Su, they performed a genetic analysis on the child and her immediate family. The study appeared online on June 12, 2017, in the Journal of Experimental Medicine.
The analysis identified a rare mutation in the IFIH1 gene, which codes for a protein called MDA5. Animal studies had found that MDA5 plays an important role in detecting viruses and initiating an immune response. The researchers showed that the child’s mutant MDA5 didn’t recognize HRV, and cells from her nasal passages weren’t able to suppress the virus.
The team confirmed that human MDA5 normally recognizes HRV. However, the protein isn’t needed to recognize and control infections by another common cold virus, respiratory syncytial virus (RSV), or flu virus. The researchers speculate that lung damage, a weakened immune system due to HRV infections, or other unknown factors may have contributed to the child’s increased infections with these other viruses.
To explore whether other people might be affected by similar mutations, the researchers analyzed a database of over 60,000 volunteers’ genomes. They found multiple rare variations in IFIH1 that could lead to less effective MDA5. Interestingly, most people with these variations lived a normal lifespan and had healthy children. Other genetic factors may have compensated for the abnormality, or people with frequent HRV infections may not have reported them.
With intensive care, the child survived numerous bouts of illness. Her health improved as her immune system matured and formed protective antibodies against various infectious agents.
This study has led to a better understanding of the human response to the common cold. Using this information, researchers hope to find a more direct way to fight HRV infections. “When people have other disease factors, HRV infection can become a tipping point and lead to severe illness, disability, or even death,” Su says. “Now that we better understand the pathway, we can investigate more targeted ways to intervene.”
“The human immune response to common cold viruses is poorly understood,” says NIAID Director Dr. Anthony S. Fauci. “By investigating this unique case, our researchers not only helped this child but also helped answer some important scientific questions about these ubiquitous infections that affect nearly everyone.”
Lamborn, I. T., Jing, H., Zhang, Y., Drutman, S. B., Abbott, J. K., Munir, S., ... & Masutani, E. (2017). Recurrent rhinovirus infections in a child with inherited MDA5 deficiency. Journal of Experimental Medicine, jem-20161759.