The PB2 Subunit of the Influenza A Virus RNA Polymerase Is Imported into the Mitochondrial Matrix.
Identifieur interne : 000C96 ( Ncbi/Checkpoint ); précédent : 000C95; suivant : 000C97The PB2 Subunit of the Influenza A Virus RNA Polymerase Is Imported into the Mitochondrial Matrix.
Auteurs : Joshua C D. Long [Royaume-Uni] ; Ervin Fodor [Royaume-Uni]Source :
- Journal of virology [ 1098-5514 ] ; 2016.
Descripteurs français
- KwdFr :
- Animaux, Fibroblastes, Microscopie électronique, Mitochondries (), Protéines adaptatrices de la transduction du signal (déficit), Protéines adaptatrices de la transduction du signal (métabolisme), Protéines virales (analyse), Protéines virales (génétique), Signaux de triage des protéines, Souris, Souris knockout, Sous-type H1N1 du virus de la grippe A (enzymologie), Transport de protéines.
- MESH :
- analyse : Protéines virales.
- déficit : Protéines adaptatrices de la transduction du signal.
- enzymologie : Sous-type H1N1 du virus de la grippe A.
- génétique : Protéines virales.
- métabolisme : Protéines adaptatrices de la transduction du signal.
- Animaux, Fibroblastes, Microscopie électronique, Mitochondries, Signaux de triage des protéines, Souris, Souris knockout, Transport de protéines.
English descriptors
- KwdEn :
- Adaptor Proteins, Signal Transducing (deficiency), Adaptor Proteins, Signal Transducing (metabolism), Animals, Fibroblasts, Influenza A Virus, H1N1 Subtype (enzymology), Mice, Mice, Knockout, Microscopy, Electron, Mitochondria (chemistry), Protein Sorting Signals, Protein Transport, Viral Proteins (analysis), Viral Proteins (genetics).
- MESH :
- chemical , analysis : Viral Proteins.
- chemical , deficiency : Adaptor Proteins, Signal Transducing.
- chemical , genetics : Viral Proteins.
- chemical , metabolism : Adaptor Proteins, Signal Transducing.
- chemistry : Mitochondria.
- enzymology : Influenza A Virus, H1N1 Subtype.
- Animals, Fibroblasts, Mice, Mice, Knockout, Microscopy, Electron, Protein Sorting Signals, Protein Transport.
Abstract
The polymerase basic 2 (PB2) subunit of the RNA polymerase complex of seasonal human influenza A viruses has been shown to localize to the mitochondria. Various roles, including the regulation of apoptosis and innate immune responses to viral infection, have been proposed for mitochondrial PB2. In particular, PB2 has been shown to inhibit interferon expression by associating with the mitochondrial antiviral signaling (MAVS) protein, which acts downstream of RIG-I and MDA-5 in the interferon induction pathway. However, in spite of a growing body of literature on the potential roles of mitochondrial PB2, the exact location of PB2 in mitochondria has not been determined. Here, we used enhanced ascorbate peroxidase (APEX)-tagged PB2 proteins and electron microscopy to study the localization of PB2 in mitochondria. We found that PB2 is imported into mitochondria, where it localizes to the mitochondrial matrix. We also demonstrated that MAVS is not required for the import of PB2 into mitochondria by showing that PB2 associates with mitochondria in MAVS knockout mouse embryo fibroblasts. Instead, we found that amino acid residue 9 in the N-terminal mitochondrial targeting sequence is a determinant of the mitochondrial import of PB2, differentiating the localization of PB2 of human from that of avian influenza A virus strains. We also showed that a virus encoding nonmitochondrial PB2 is attenuated in mouse embryonic fibroblasts (MEFs) compared with an isogenic virus encoding mitochondrial PB2, in a MAVS-independent manner, suggesting a role for PB2 within the mitochondrial matrix. This work extends our understanding of the interplay between influenza virus and mitochondria.
DOI: 10.1128/JVI.01384-16
PubMed: 27440905
Affiliations:
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pubmed:27440905Le document en format XML
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<front><div type="abstract" xml:lang="en">The polymerase basic 2 (PB2) subunit of the RNA polymerase complex of seasonal human influenza A viruses has been shown to localize to the mitochondria. Various roles, including the regulation of apoptosis and innate immune responses to viral infection, have been proposed for mitochondrial PB2. In particular, PB2 has been shown to inhibit interferon expression by associating with the mitochondrial antiviral signaling (MAVS) protein, which acts downstream of RIG-I and MDA-5 in the interferon induction pathway. However, in spite of a growing body of literature on the potential roles of mitochondrial PB2, the exact location of PB2 in mitochondria has not been determined. Here, we used enhanced ascorbate peroxidase (APEX)-tagged PB2 proteins and electron microscopy to study the localization of PB2 in mitochondria. We found that PB2 is imported into mitochondria, where it localizes to the mitochondrial matrix. We also demonstrated that MAVS is not required for the import of PB2 into mitochondria by showing that PB2 associates with mitochondria in MAVS knockout mouse embryo fibroblasts. Instead, we found that amino acid residue 9 in the N-terminal mitochondrial targeting sequence is a determinant of the mitochondrial import of PB2, differentiating the localization of PB2 of human from that of avian influenza A virus strains. We also showed that a virus encoding nonmitochondrial PB2 is attenuated in mouse embryonic fibroblasts (MEFs) compared with an isogenic virus encoding mitochondrial PB2, in a MAVS-independent manner, suggesting a role for PB2 within the mitochondrial matrix. This work extends our understanding of the interplay between influenza virus and mitochondria.</div>
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