August 14, 2017Infectious Disease
Colds contribute to more than 18 billion upper respiratory infections worldwide each year, according to the Global Burden of Disease Study. According to an article published online in the Journal of Experimental Medicine (12 June 2017), a rare genetic mutation has been identified that results in a markedly increased susceptibility to infection by human rhinoviruses (HRVs) -- the main causes of the common cold. The rare mutation was identified in a young child with a history of severe HRV infections. Several weeks after birth, the child began experiencing life-threatening respiratory infections, including colds, influenza and bacterial pneumonia. Because her physicians suspected she might have a primary immune deficiency - a genetic abnormality affecting her immune system - they performed a genetic analysis. The analysis revealed that she had a mutation in the IFIH1 gene that caused her body to make dysfunctional MDA5 proteins in cells in her respiratory tract. Previously, it was found that laboratory mice lacking functional MDA5 could not detect genetic material from several viruses, making them unable to launch appropriate immune responses against them. Similarly, the authors found that mutant MDA5 in the girl's respiratory tissues could not recognize HRVs, preventing her immune system from producing protective signaling proteins called interferons. HRV thus replicated unchecked in the girl's respiratory tract, causing severe illness. These observations led the authors to conclude that functional MDA5 is critical to protecting people against HRV. Fortunately, with intensive care, the child survived numerous bouts of severe illness, and her health has improved as her immune system matured and formed protective antibodies against various infectious agents.
To explore whether other people experience poor health related to the IFIH1 gene, the authors analyzed a database of over 60,000 volunteers' genomes. While rare, the team found multiple variations in IFIH1 that could lead to less effective MDA5. Interestingly, most people with these variations lived normal lifespans and had healthy children, leading the authors to suspect that other genetic factors may have compensated for the abnormality, or that people experienced frequent HRV infections but did not report them. The Centers for Disease Control and Prevention estimates the average healthy adult has about 2 to 3 colds per year, but the range varies widely based on lifestyle and environment. For most people, infection with HRVs leads to minor illness that does not require medical attention, but the viruses can cause serious complications in people with severe asthma, chronic obstructive pulmonary disease, and other health problems. However, no antiviral therapies exist for HRVs, so these patients -- like the child in the study -- receive supportive care and are advised to take steps to avoid exposure. Insights from this study may lead to new strategies for treating patients with severe HRV complications and inadequate MDA5 responses.