PB1F2

PB1F2, also written PB1-F2, is a small protein produced by certain influenza A viruses from an alternative reading frame within the PB1 gene segment. It is typically about 87 to 90 amino acids in length, though many isolates contain stop codons that shorten or abolish the protein. Expression depends on the integrity of the alternative open reading frame and its initiation site.

Localization and structure: PB1-F2 is associated with mitochondria, aided by an N-terminal mitochondrial targeting sequence. The protein is thought to interact with mitochondrial membranes, with the C-terminal region contributing to membrane association and function. Its exact structure is not uniform across strains, reflecting sequence variability.

Function and effects on the host: PB1-F2 is pro-apoptotic and can promote mitochondria-mediated cell death, which may contribute to tissue damage during infection. It has been shown to interact with mitochondrial proteins such as ANT3 and VDAC1, promoting mitochondrial permeabilization and cytochrome c release in some contexts. In addition to apoptosis, PB1-F2 can modulate innate immune responses and influence dendritic cell function and cytokine production. The magnitude and nature of these effects are highly dependent on the viral strain and host species.

Role in virulence and evolution: In several animal models, PB1-F2 expression has been associated with increased virulence and disease severity for particular influenza A strains, while deletions or truncations of PB1-F2 can reduce virulence in those contexts. A well-studied polymorphism at residue 66 (N66S) has been linked to enhanced pathogenicity and altered host responses in some strains, though findings are not universal across all lineages.

Overall, PB1-F2 is an accessory viral protein with strain-dependent contributions to pathogenicity, apoptosis, and immune modulation, rather than a universally essential factor for influenza A replication.