Genes Could Increase Likelihood of Developing Common Cold

Mutated MDA5 may not recognize human rhinoviruses.

A majority of individuals develop the common cold each year through infection with human rhinoviruses (HRVs). More than 18 million upper respiratory infections develop due to colds annually.

Investigators in a new case study have discovered a genetic mutation that can increase susceptibility to the common cold. The study, published by the Journal of Experimental Medicine, shows an underlying mechanism used by the immune system to respond to HRVs.

Just weeks after birth, the study subject began developing life-threatening respiratory infections, including colds, influenza, and bacterial pneumonia. The child’s physicians hypothesized she had an immune deficiency, so they conducted a genetic analysis.

The genetic analysis revealed a mutation in the IFIH1 gene that resulted in dysfunctional MDA5 proteins in respiratory tract cells, according to the study.

Previous studies showed that mice lacking MDA5 were unable to detect genetic material from multiple viruses, meaning that the immune system did not initiate a proper attack.

In the current study, the authors discovered that the mutated MDA5 protein failed to recognize HRVs. This was observed to prevent the patient’s immune system from producing interferons, a protective signaling protein, according to the study.

HRV was able to replicate without immune attack in the respiratory tract and resulted in numerous infections. These findings caused researchers to determine that MDA5 is crucial to the attack against HRV.

“The human immune response to common cold viruses is poorly understood,” said Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Disease (NIAID). “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.”

To determine if a mutated IFIH1 gene affected the health of other patients, the investigators then analyzed the genomes of 60,000 individuals.

The authors discovered multiple IFIH1 genetic mutations that resulted in less effective MDA5; however, the mutations were rare. They reported that a majority of these patients had normal lives and had healthy children. These findings suggest that other factors may have led to an increased susceptibility to HRV or incidence of HRV was underreported, according to the study.

The CDC reports that the average adult experiences 2 to 3 colds per year, but lifestyle and environment plays a role. For a majority of individuals, HRV infections are minor, but can cause serious events in patients with asthma, COPD, and other health issues. Currently, no antiviral drugs exist for HRVs, so patients with the conditions must receive supportive care and should limit potential exposure to the virus, according to the study.

The investigators believe that these findings may lead to novel approaches to treat patients with HRV complications and limited MDA5 response.

“When people have other disease factors, HRV infection can become a tipping point and lead to severe illness, disability or even death,” said senior author Helen Su, MD, PhD, chief of the Human Immunological Diseases Section of the Laboratory of Host Defenses in NIAID’s Department of Intramural Research. “Now that we better understand the pathway, we can investigate more targeted ways to intervene.”