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Flu virus wipes out immune system's first responders to establish infection
Date:10/20/2013

rus-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 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," says Dougan. "This is actually a perfect model for studying memory immune cells."

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."


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Contact: Matt Fearer
fearer@wi.mit.edu
617-452-4630
Whitehead Institute for Biomedical Research
Source:Eurekalert

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