Flu virus wipes out immune system's first responders to establish infection

October 20, 2013, Whitehead Institute for Biomedical Research

Revealing influenza's truly insidious nature, Whitehead Institute scientists have discovered that the virus is able to infect its host by first killing off the cells of the immune system that are actually best equipped to neutralize the virus.

Confronted with a harmful virus, the works to generate cells capable of producing antibodies perfectly suited to bind and disarm the hostile invader. These virus-specific B cells proliferate, secreting the antibodies that slow and eventually eradicate the virus. A population of these cells retains the information needed to neutralize the virus and takes up residence in the lung to ward off secondary infection from re-exposure to the virus via inhalation.

On the surface of these so-called memory B cells are high-affinity virus-specific receptors that bind to reduce viral spread. While such cells should serve at the body's first line of defense, it turns out that 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 has to establish infection," says Joseph Ashour, a co-author of the Nature paper and a postdoctoral researcher in the lab of Whitehead Member Hidde Ploegh.

"This is how the virus gains a foothold," adds Ploegh lab postdoc Stephanie Dougan, also a co-author of the study. "The virus targets in the lung, which allows infection to be established—even if the immune system has seen this flu before."

Discovering this dynamic of the virus was no small task, in part because virus-specific B cells are found in exceedingly small numbers and are extremely difficult to isolate. To overcome these challenges, 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 , 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 , 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," says Dougan. "This is actually a perfect model for studying memory immune ."

Adds Ashour: "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."

Explore further: Researchers discover a new way that influenza can infect cells

More information: "Antigen-specific B- cell receptor sensitizes B cells to infection by influenza virus" Nature, October 20, 2013. DOI: 10.1038/nature12637

Related Stories

Researchers discover a new way that influenza can infect cells

September 23, 2013
Scientists at Fred Hutchinson Cancer Research Center have uncovered a new mechanism by which influenza can infect cells – a finding that ultimately may have implications for immunity against the flu.

Scientists closer to universal flu vaccine after pandemic 'natural experiment'

September 22, 2013
Scientists have moved closer to developing a universal flu vaccine after using the 2009 pandemic as a natural experiment to study why some people seem to resist severe illness.

Two-pronged immune cell approach could lead to universal shot against flu

March 14, 2013
Seasonal epidemics of influenza result in nearly 36,000 deaths annually in the United States, according to the Centers for Disease Control. Current vaccines against the influenza virus elicit an antibody response specific ...

Immune system discovery could lead to EBV vaccine to prevent mono, some cancers

October 11, 2013
Development of a vaccine against Epstein-Barr virus (EBV) has taken a step forward with the Canadian discovery of how EBV infection evades detection by the immune system.

Researchers suggest boosting body's natural flu killers

May 23, 2013
A known difficulty in fighting influenza (flu) is the ability of the flu viruses to mutate and thus evade various medications that were previously found to be effective. Researchers at the Hebrew University of Jerusalem have ...

Researchers discover how some natural antibodies are able to stop flu

February 11, 2013
(Medical Xpress)—Researchers with the Scripps Institute have discovered that three naturally occurring antibodies are able to overcome flu mutations by attaching to a non-changing protein in the flu virus. As they describe ...

Recommended for you

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

Secrets of longevity protein revealed in new study

January 17, 2018
Named after the Greek goddess who spun the thread of life, Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, researchers revealed the three-dimensional structure ...

The HLF gene protects blood stem cells by maintaining them in a resting state

January 17, 2018
The HLF gene is necessary for maintaining blood stem cells in a resting state, which is crucial for ensuring normal blood production. This has been shown by a new research study from Lund University in Sweden published in ...

Magnetically applied MicroRNAs could one day help relieve constipation

January 17, 2018
Constipation is an underestimated and debilitating medical issue related to the opioid epidemic. As a growing concern, researchers look to new tools to help patients with this side effect of opioid use and aging.

Researchers devise decoy molecule to block pain where it starts

January 16, 2018
For anyone who has accidentally injured themselves, Dr. Zachary Campbell not only sympathizes, he's developing new ways to blunt pain.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.