Rare Genetic Mutation Can Increase Susceptibility to Human Rhinoviruses

Millions of individuals in the United States catch the common cold each year. Although many viruses can cause the common cold, one of the key players responsible for these colds are human rhinoviruses (HRVs). For some, recovery time can range from a week to 10 days; however, others are not as lucky and these colds can develop into much more severe illnesses.

However, researchers are learning more about these viruses each day. In fact, in a recent case study published online in the Journal of Experimental Medicine, National Institute of Allergy and Infectious Diseases (NIAID) researchers have discovered a rare genetic mutation that “markedly increases” an individual’s susceptibility for infection with HRVs. Furthermore, the case has also shed light on “an important mechanism by which the immune system responds to these viruses,” according to a recent press release.

This specific case entailed a female child who, just several weeks after birth, struggled with severe, “life-threatening respiratory infections,” such as colds, flu, and bacterial pneumonia. The physicians treating her surmised that she may be suffering from a “primary immune deficiency,” and thus, decided to perform a genetic analysis.

Their findings? The girl’s IFIH1 gene was mutated, prompting her body to produce “dysfunctional MDA5 proteins” in the cells within her respiratory tract.

In previous research involving laboratory mice, these researchers found that the mice that had mutant MDA5 proteins were not able to “detect genetic material from several viruses,” and due to this, their immune system was unable to respond accordingly. Much in the same vein, the scientists found that the mutant MDA5 proteins within the girl’s respiratory tract were not able to recognize HRVs, and thus, her immune system was unable to produce the interferons, or “protective signaling proteins” needed to prompt immune response. These findings led them to conclude that when it comes to achieving protection against HRVs, functional MDA5 proteins are imperative.

The scientists report that the girl went on to “survive numerous bouts of severe illness” while in intensive care, and, as her immune system matured, it became capable of producing “protective antibodies against various infectious agents.”

“The human immune response to common cold viruses is poorly understood,” NIAID Director, Anthony S. Fauci, MD, shared in a press release. “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.”

The scientists took their research a step further to find out if variations to the IFIH1 gene was responsible for poor health in other patients as well. By looking at more than 60,000 volunteers’ genomes within a database, the scientists found that, albeit rare, there were multiple variations of the IFIH1 gene that could result in “less effective” MDA5 proteins. However, interestingly enough, they also found that the majority of those with these variations were still living normal lifespans and bearing healthy children. Due to this, researchers hypothesized that other genetic factors may be at play that may have “compensated for the abnormality,” or that those recurrently experiencing HRVs might be failing to report them.

On average, an adult will catch a cold about 2 to 3 times per year. Most individuals will have to deal with the pesky common associated symptoms (such as sore throat, runny nose, coughing, and sneezing), but for others, these colds can result in more serious, potentially life-threatening illnesses. There is no cure for the cold—no antiviral therapies exist. However, NIAID scientists hope that this research could, down the line, lead to new treatment options for these patients, who experience HRV-associated complications and ineffective MDA5 protein response.

“When people have other disease factors, HRV infection can become a tipping point and lead to severe illness,” study 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, concluded. “Now that we better understand the pathway, we can investigate more targeted ways to intervene.”