A novel influenza A virus mitochondrial protein that induces cell death

While searching for alternative reading-frame peptides encoded by influenza A virus that are recognized by CD8(+)T cells, we found an abundant immunog enic peptide encoded by the +1 reading frame of PB1. This peptide derives f rom a novel conserved 87-residue protein, PB1-F2, which has several unusual features compared with other influenza gene products in addition to its mo de of translation. These include its absence from some animal (particularly swine) influenza virus Isolates, variable expression in individual infecte d cells, rapid proteasome-dependent degradation and mitochondrial localizat ion. Exposure of cells to a synthetic version of PB1-F2 induces apoptosis, and influenza viruses with targeted mutations that interfere with PB1-F2 ex pression Induce less extensive apoptosis in human monocytic cells than thos e with intact PB1-F2. We propose that PB1-F2 functions to kill host immune cells responding to influenza virus infection.