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’s immunity.
“Our bodies have an impressive network of immune cells; they work together to detect viruses and trigger immune responses that limit — or prevent — disease,” says Dr. Andrew Makrigiannis, head of Dalhousie’s 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.
“In 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,” says Dr. Makrigiannis. “We also found that influenza virus infection causes changes to the surface of infected cells, which prevent many of these NK cells from detecting them.”
Researchers now know that NK cells play a lead role in preventing the development of the flu.
“It’s 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 — and more importantly, what we can do to stop this from happening.”
“We’ve discovered a unique mechanism by which flu virus can hide and replicate inside an infected cell without being destroyed,” explains Mahmoud. “By interfering with this process, we managed to enhance the ability of the NK cell to recognize and destroy infected cells faster.”
Figuring out how influenza viruses ‘hide’ 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.
“Our immune cells are trained to identify and destroy virus-infected cells,” explains Dr. Craig McCormick, associate professor in the Department of Microbiology & Immunology. “However, they don’t always work as well as they should. Our study revealed novel mechanisms that the influenza virus uses to escape detection by our immune system.”
Dr. Denys Khaperskyy, senior research associate in Dr. McCormick’s 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.
“Every year the immune system is challenged to fight off new influenza viruses,” says Dr. Khaperskyy. “And one of the ways that the virus escapes detection by the immune system is by rapidly changing from one flu season to the next.
“Now 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’t 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.”
Dal’s emerging strength in influenza research
“As 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,” says Dr. Makrigiannis. “Now the major task is to understand how it can do this.”
Dalhousie has a collaborative team of scientists and clinicians who are working on finding and developing better antivirals against the flu.
“It’s exciting times for influenza virus research, and Dalhousie Medical School is on the forefront of this area of investigation,” says Dr. Gerry Johnston, the medical school’s associate dean of research. “Our researchers are looking at immune evasion by influenza virus at the cellular, molecular, and genetic levels. We’ve got all areas covered.”
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.