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“Hidden” Protein May Explain Why Some Flus Are More Dangerous than Others

Sometimes, it's the small, silent types that cause the most trouble.

Flu protein migrates to cell mitochondria photo
The PB1-F2 protein (green) migrates to the mitochondria (red) resulting in the color yellow in this computer-generated image of an influenza virus-infected cell. PB1-F2 compromises mitochondrial function, which leads to cell death.
Credit: NIAID

A small protein encoded by a newly discovered, camouflaged gene for the type A flu virus may kill immune system cells that fight the virus, say Jon Yewdell, M.D., Ph.D., and Jack Bennink, Ph.D., researchers in the NIAID Laboratory of Viral Diseases. Their finding could one day explain why some flu strains are more deadly than others.

Drs. Yewdell and Bennink stumbled upon the protein by luck while trying to determine if "junk" peptides, short scraps of protein that a virus manufactures by accident as it makes copies of itself, could be recognized by the immune system. The new protein, named PB1-F2, had never before been detected because the gene that encodes it overlaps the much larger PB1 gene.

Using a technique called immunofluorescence, which makes the protein glow green under a laser microscope, the team found that the protein targets the mitochondria of its host cell, speeding the cell's demise. Other experiments suggest that PB1-F2 may also be secreted by infected cells to kill immune cells rushing to the site of infection, multiplying its deadly effects.

The team is also studying whether this toxic protein played a role in the 1918 Spanish flu pandemic in which more than 20 million people, many between the ages of 18 and 30, died around the world.


W Chen et al. A novel influenza A virus mitochondrial protein that induces cell death. Nat Med 7(12):1306-12. DOI: 10.1038/nm1201-1306 (2001).

Last Updated March 12, 2013

Last Reviewed March 12, 2013