The Flu Virus is More Insidious Than Originally Thought

Flu virus illustration via Shutterstock

Scientists at MIT’s Whitehead Institute have discovered that the flu virus is more insidious than we think. The researchers found that the virus is able to infect its host by killing off the cells of the immune system that are actually best equipped to handle the virus. Their findings were published in an October issue of the journal, Nature.

When the immune system is confronted with a harmful virus, it will generate cells that are capable of producing antibodies to attack the virus. These virus-specific B cells rapidly increase in numbers and discharge the antibodies necessary to slow and eventually eradicate the virus. A population of these cells retain the information needed to neutralize the virus and move to the lungs to ward off any secondary infection from re-exposure to the virus via inhalation.

The Whitehead Institute explains the study further in a report:

On the surface of these so-called memory B cells are high-affinity virus-specific receptors that bind virus particles to reduce viral spread. While such cells should serve at the body’s first line of defense, it turns out that flu virus exploits the specificity of the cells’ receptors, using them to gain entry, disrupt antibody production, and ultimately kill the cells. By dispatching its enemies in this fashion, the virus is able to replicate efficiently before the immune system can mount a second wave of defense. This seemingly counter-intuitive pathway to infection is described this week in the journal Nature.

“We can now add this to the growing list of ways that the flu virus has to establish infection,” says Joseph Ashour, a co-author of the Nature paper and a postdoctoral researcher. “This is research that could help with rational vaccine design, leading to more effective vaccines for seasonal flu. It might even suggest novel strategies for conferring immunity.”

Postdoc researcher Stephanie Dougan, also a co-author of the study, says that the virus targets memory cells in the lung. “[This] allows infection to be established—even if the immune system has seen this flu before,” she says.

The Whitehead Institute also says this kind of study was no small task because virus-specific B cells are found in exceedingly small numbers and are incredibly difficult to isolate. The Institute explains in the report exactly how did it:

Dougan together with students Max Popp and Roos Karssemeijer leveraged a protein-labeling technology developed earlier in the Ploegh lab to attach a fluorescent label to influenza virus, thus identifying flu-specific B cells by their interaction with fluorescent flu micelles. This step was essential because no flu protein can be tagged in the conventional manner with green fluorescent protein (GFP) in the context of an infectious virus. Dougan then introduced the B cells’ nuclei into enucleated mouse egg cells via somatic cell nuclear transfer (SCNT)—a cloning technique she learned in Whitehead Founding Member Rudolf Jaenisch’s lab—to generate a line of mice with virus-specific B cells and cell receptors.

Though complicated, the generation of mice with B cells specific for a known pathogen allowed Dougan and Ashour to track the virus’s interactions with the cells in unprecedented fashion. Because the infectious process they discovered is likely not exclusive to influenza virus, these scientists believe their approach could have implications for other viruses as well.

“We can now make highly effective immunological models for a variety of pathogens,” Dougan says. “This is actually a perfect model for studying memory immune cells.”