A novel influenza A virus mitochondrial protein that induces cell death

Weisan Chen, Paul A. Calvo, Daniela Malide, James Gibbs, Ulrich Schubert, Igor Bacik, Sameh Basta, Robert O'Neill, Jeanne Schickli, Peter Palese, Peter Henklein, Jack R. Bennink, Jonathan W. Yewdell

Research output: Contribution to journalArticlepeer-review

831 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1306-1312
Number of pages7
JournalNature Medicine
Volume7
Issue number12
DOIs
StatePublished - 2001

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