Mitochondrial targeting sequence of the influenza A virus PB1-F2 protein and its function in mitochondria

Hiroshi Yamada1, Ritsu Chounan, Youichirou Higashi

  • 1Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Kuramoto-cho 3-18-15, 770-8503, Japan.

FEBS Letters
|December 14, 2004
PubMed

Insights

The influenza A virus PB1-F2 protein targets mitochondria, altering their structure and function. Specific regions of PB1-F2, particularly residues 63-75, are crucial for this mitochondrial localization.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Influenza A virus is a significant human pathogen.
  • The role of the PB1-F2 protein in viral pathogenesis is not fully understood.
  • PB1-F2 is known to interact with host cell components.

Purpose of the Study:

  • To determine the region of the PB1-F2 protein responsible for mitochondrial targeting.
  • To investigate the effects of PB1-F2 on mitochondrial morphology and function.

Main Methods:

  • Construction and transfection of PB1-F2 deletion mutants and site-directed mutants.
  • Localization studies using 3xFLAG-tagged PB1-F2.
  • Microscopy to assess mitochondrial morphology.
  • Measurement of mitochondrial inner-membrane potential.

Main Results:

  • The domain spanning residues 46-75 of PB1-F2 is necessary and sufficient for mitochondrial targeting.
  • A smaller subdomain (residues 63-75) and specific basic residues (Lys73, Arg75) are minimally required for localization.
  • PB1-F2 expression altered mitochondrial morphology from filamentous to dotted structures.
  • PB1-F2 suppressed the mitochondrial inner-membrane potential.

Conclusions:

  • The PB1-F2 protein contains a specific domain that directs it to the mitochondria.
  • PB1-F2 influences mitochondrial structure and function, potentially impacting viral replication and host cell response.

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