Severe flu may strike people with defective viral warning proteins

The flu, or influenza, is a seasonal respiratory infection that targets the lungs. Influenza can result in a fever, cough, runny nose, congestion, and headaches. In some people, the symptoms are so severe that they become confined to a bed for weeks and may go on to develop pneumonia or acute respiratory distress syndrome (ARDS, severe inflammation of the lungs). In 2014, 4,605 people in the US died from the flu or complications associated with it. We know that certain diseases, like COPD or asthma, and old age can predispose someone to having more severe flu infections but we don’t know whether there are genetic alterations that predispose someone to developing a severe infection. In a case report published bya group of researchers from New York, one such genetic alteration in a young girl may have caused her to develop a life threatening influenza infection.

The 2.5-year-old girl was infected with the H1N1 strain of the flu and hospitalized for life-threatening ARDS. The girl had no predisposing condition that could make her more likely to get a severe infection (like asthma) and had never been infected with the H1N1 virus before. When the researchers looked at her DNA they found two different mutations in one gene, IRF7. These two mutations were inherited from her mother and father, one from each. The parents did not appear to have any negative outcomes from their mutation.Only when the two mutations were combined in the child did a problem arise. The gene, IRF7 or interferon regulatory factor 7, is a key regulator of the immune systems response to viruses. IRF7 instructs the cells to make a protein call interferon (IFN). This protein is released by cells that are infected by a virus and acts as a warning to other cells in the area that a virus is present. In response to the IFN, cells boost their immune defences so as to better fight off the infection. This is similar to when security is enhanced at an event when police suggest that something might happen. If a person does not have enough IFN it would make them more susceptible to viral infections and make it harder for the body to fight the infection. The researchers found that the immune cells from this girl did not make enough IFN in response to the H1N1. Also, her immune cells could not make dozens of other proteins important in fighting off the virus. These defects resulted in her infection becoming so serious that she needed to be hospitalized.

This case-report suggests that mutations in genes important in the immune response to viruses could be behind many of the severe or fatal cases of influenza in the world. These mutations may be normally are harmless and not show up until a person is exposed to a virus like H1N1. Screening of patients in hospital with severe infections may help us determine an appropriate course of action to help them fight off the virus. Interestingly, this gene mutation does not render the flu vaccine ineffective since this same girl, now 7, is protected from most influenza infections thanks to a seasonal flu vaccine.

Photo Credit: Flickr Matthew Perkins