Characterization of a mitochondrial-targeting signal in the PB2 protein of influenza viruses

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Influenza virus RNA polymerase, crucial for viral replication, comprises PB1, PB2, and PA subunits.
• These subunits typically localize to the nucleus in infected cells.

Purpose of the Study:

• To investigate the subcellular localization of influenza virus PB2 subunit beyond the nucleus.
• To determine the role of PB2 mitochondrial localization in influenza virus infection.

Main Methods:

• Transfection of cells with PB2 constructs.
• Infection of cells with influenza A virus.
• Site-directed mutagenesis of PB2 protein.
• Analysis of viral titers, gene expression, and mitochondrial membrane potential.

Main Results:

• PB2 subunit from human and avian influenza viruses localizes to mitochondria in transfected and infected cells.
• An N-terminal 120-amino acid motif in PB2, with specific leucine residues (L7, L10), is essential for mitochondrial targeting.
• Mutations L7A and/or L10A in recombinant influenza viruses reduced viral titers but did not affect transcription, replication, or protein expression.
• These mutations correlated with reduced mitochondrial membrane potential in infected cells.

Conclusions:

• Mitochondrial localization of influenza virus PB2 is a novel finding with implications for viral pathogenesis.
• PB2 targeting to mitochondria, mediated by specific N-terminal residues, may contribute to preserving mitochondrial function during infection.
• This interaction could represent a new target for antiviral strategies.