Characterization of a mitochondrial-targeting signal in the PB2 protein of influenza viruses.
Influenza virus RNA polymerase is a heterotrimeric complex consisting of PB1, PB2, and PA subunits. These polymerase subunits accumulate in the nucleus of infected cells. We report here that PB2, from both human and avian influenza viruses, could also localize to mitochondria in transfected cells. Importantly, cells infected with influenza A virus also displayed mitochondrial PB2. We show that an N-terminal motif composed of 120 amino acids is sufficient for localization of PB2 to mitochondria. In particular, leucine residues at positions 7 and 10 were essential for mitochondrial targeting. Recombinant influenza A/WSN/33 viruses expressing PB2 proteins with L7A and/or L10A mutations showed reduced viral titers, but unaffected levels of transcription, replication, and protein expression. The introduction of L7A and/or L10A mutations into recombinant viruses correlated with reduced mitochondrial membrane potential in infected cells, suggesting that mitochondrial localization of PB2 contributes to the preservation of mitochondrial function during influenza virus infection.
Carr
Simon M
SM
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.
Carnero
Elena
E
García-Sastre
Adolfo
A
Brownlee
George G
GG
Fodor
Ervin
E
D000818:Animals; D002460:Cell Line; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000378:metabolism*; D009976:Orthomyxoviridae Infections / Q000821:virology; D017354:Point Mutation; D011485:Protein Binding; D021382:Protein Sorting Signals / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport; D019562:Viral Load; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C502893:PB2 protein, influenza virus; D021382:Protein Sorting Signals; D014764:Viral Proteins