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 immunogenic peptide encoded by the +1 reading frame of PB1. This peptide derives from a novel conserved 87-residue protein, PB1-F2, which has several unusual features compared with other influenza gene products in addition to its mode of translation. These include its absence from some animal (particularly swine) influenza virus isolates, variable expression in individual infected cells, rapid proteasome-dependent degradation and mitochondrial localization. Exposure of cells to a synthetic version of PB1-F2 induces apoptosis, and influenza viruses with targeted mutations that interfere with PB1-F2 expression induce less extensive apoptosis in human monocytic cells than those with intact PB1-F2. We propose that PB1-F2 functions to kill host immune cells responding to influenza virus infection.
Chen
W
W
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
Calvo
P A
PA
Malide
D
D
Gibbs
J
J
Schubert
U
U
Bacik
I
I
Basta
S
S
O'Neill
R
R
Schickli
J
J
Palese
P
P
Henklein
P
P
Bennink
J R
JR
Yewdell
J W
JW
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D017124:Conserved Sequence; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D009842:Oligopeptides / Q000235:genetics / Q000494:pharmacology; D016366:Open Reading Frames; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D014176:Protein Biosynthesis; D021381:Protein Transport; D013045:Species Specificity; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D024101:Mitochondrial Proteins; D009097:Multienzyme Complexes; D009842:Oligopeptides; C442816:PB1-F2 protein, Influenza A virus; D010446:Peptide Fragments; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex