Dalhousie Medical School researchers have made two discoveries that shine light on how influenza is detected by the immune system, and how the virus has evolved to undermine the body鈥檚 immunity.
鈥淥ur bodies have an impressive network of immune cells; they work together to detect viruses and trigger immune responses that limit 鈥� or prevent 鈥� disease,鈥� says Dr. Andrew Makrigiannis, head of Dalhousie鈥檚 Department of Microbiology & Immunology.
A special kind of immune cell known as the natural killer cell (or NK cell for short) is often the first to detect and destroy virus-infected cells. It then sends signals to coordinate follow-up responses to resolve infection.
A NK cell expert, Dr. Makrigiannis was recently recruited back to Halifax from the University of Ottawa.
鈥淚n a study led by my PhD student Ahmad Mahmoud, our Ottawa lab discovered new properties of NK cells that allow them to control influenza virus infection,鈥� says Dr. Makrigiannis. 鈥淲e also found that influenza virus infection causes changes to the surface of infected cells, which prevent many of these NK cells from detecting them.鈥�
Researchers now know that NK cells play a lead role in preventing the development of the flu.
鈥淚t鈥檚 clear that NK cells usually protect us from the flu virus. But in some unlucky individuals, the virus manages to fool the immune system. Our research gives us important insight into one of the ways the virus tricks NK cells 鈥� and more importantly, what we can do to stop this from happening.鈥�
鈥淲e鈥檝e discovered a unique mechanism by which flu virus can hide and replicate inside an infected cell without being destroyed,鈥� explains聽 Mahmoud. 鈥淏y interfering with this process, we managed to enhance the ability of the NK cell to recognize and destroy infected cells faster.鈥�
Figuring out how influenza viruses 鈥榟ide鈥� from our immune system
Another team of Dalhousie Medical School researchers has figured out how the influenza virus can prevent detection of infected cells and the initiation of immune responses.
鈥淥ur immune cells are trained to identify and destroy virus-infected cells,鈥� explains Dr. Craig McCormick, associate professor in the Department of Microbiology & Immunology. 鈥淗owever, they don鈥檛 always work as well as they should. Our study revealed novel mechanisms that the influenza virus uses to escape detection by our immune system.鈥�
Dr. Denys Khaperskyy, senior research associate in Dr. McCormick鈥檚 laboratory, found that the flu virus prevents the infected cell from sending out protein-based warning signals to neighbouring cells by selective destruction of precursor molecules.
鈥淓very year the immune system is challenged to fight off new influenza viruses,鈥� says Dr. Khaperskyy. 鈥淎nd one of the ways that the virus escapes detection by the immune system is by rapidly changing from one flu season to the next.
鈥淣ow we also know that influenza virus alters the infected cells in ways that the immune system is not alerted to the infection. This allows the virus enough time to replicate and spread to the neighbouring cells. While we can鈥檛 stop the virus from changing, we might be able to stop it from altering the infected cells, thereby making them visible to the immune cells again.鈥�
Dal鈥檚 emerging strength in influenza research
鈥淎s significant as these findings are, revealing the ways that the influenza virus can escape detection by our immune cells is only the tip of the iceberg,鈥� says Dr. Makrigiannis. 鈥淣ow the major task is to understand how it can do this.鈥�
Dalhousie has a collaborative team of scientists and clinicians who are working on finding and developing better antivirals against the flu.
鈥淚t鈥檚 exciting times for influenza virus research, and Dalhousie Medical School is on the forefront of this area of investigation,鈥� says Dr. Gerry Johnston, the medical school鈥檚 associate dean of research. 鈥淥ur researchers are looking at immune evasion by influenza virus at the cellular, molecular, and genetic levels. We鈥檝e got all areas covered.鈥�
Both Dr. Makrigiannis and Dr. McCormick are funded by the Canadian Institutes of Health Research. Their studies were recently published in PLoS Pathogens, the leading journal in the field.