Article ; Online: Actin and RIG-I/MAVS signaling components translocate to mitochondria upon influenza A virus infection of human primary macrophages.
Journal of immunology (Baltimore, Md. : 1950)
2009 Volume 182, Issue 9, Page(s) 5682–5692
Abstract: ... in human macrophages. Macrophages were infected with influenza A virus, after which the cytosolic and ... interacts with mitochondria to regulate both antiviral and cell death signals during influenza A virus ... onto the mitochondria. Cytochalasin D, a potent inhibitor of actin polymerization, clearly inhibited influenza A virus ...
| Abstract | Influenza A virus is one of the most important causes of respiratory infection. During viral infection, multiple cell signaling cascades are activated, resulting in the production of antiviral cytokines and initiation of programmed cell death of virus-infected cells. In the present study, we have used subcellular proteomics to reveal the host response to influenza A infection at the protein level in human macrophages. Macrophages were infected with influenza A virus, after which the cytosolic and mitochondrial cell fractions were prepared and analyzed by using two-dimensional electrophoresis for protein separation and mass spectrometry for protein identification. In cytosolic proteomes, the level of several heat shock proteins and fragments of cytoskeletal proteins was clearly up-regulated during influenza A virus infection. In mitochondrial proteomes, simultaneously with the expression of viral proteins, the level of intact actin and tubulin was highly up-regulated. This was followed by translocation of the components of antiviral RNA recognition machinery, including RIG-I (retinoic acid-inducible protein I), TRADD (TNFR1-associated death domain protein), TRIM25 (tripartite motif protein 25), and IKKepsilon (inducible IkappaB kinase), onto the mitochondria. Cytochalasin D, a potent inhibitor of actin polymerization, clearly inhibited influenza A virus-induced expression of IFN-beta, IL-29, and TNF-alpha, suggesting that intact actin cytoskeleton structure is crucial for proper activation of antiviral response. At late phases of infection mitochondrial fragmentation of actin was seen, indicating that actin fragments, fractins, are involved in disruption of mitochondrial membranes during apoptosis of virus-infected cells. In conclusion, our results suggest that actin network interacts with mitochondria to regulate both antiviral and cell death signals during influenza A virus infection. |
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| MeSH term(s) | Actins/metabolism ; Actins/physiology ; Adaptor Proteins, Signal Transducing/metabolism ; Adaptor Proteins, Signal Transducing/physiology ; Apoptosis/immunology ; Cells, Cultured ; Cytoplasm/chemistry ; Cytoplasm/immunology ; Cytoplasm/metabolism ; DEAD Box Protein 58 ; DEAD-box RNA Helicases/metabolism ; DEAD-box RNA Helicases/physiology ; Humans ; Influenza A Virus, H3N2 Subtype/immunology ; Influenza, Human/immunology ; Influenza, Human/metabolism ; Macrophages/immunology ; Macrophages/metabolism ; Macrophages/pathology ; Macrophages/virology ; Mitochondrial Proteins/metabolism ; Mitochondrial Proteins/physiology ; Protein Array Analysis ; Protein Transport/immunology ; Proteome/biosynthesis ; Proteome/chemistry ; Proteome/immunology ; Receptors, Immunologic ; Signal Transduction/immunology ; Up-Regulation/immunology | ||||||||||
| Chemical Substances | Actins ; Adaptor Proteins, Signal Transducing ; MAVS protein, human ; Mitochondrial Proteins ; Proteome ; Receptors, Immunologic ; RIGI protein, human (EC 3.6.1.-) ; DEAD Box Protein 58 (EC 3.6.4.13) ; DEAD-box RNA Helicases (EC 3.6.4.13) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2009-04-20 | ||||||||||
| Publishing country | United States | ||||||||||
| Document type | Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't | ||||||||||
| ZDB-ID | 3056-9 | ||||||||||
| ISSN | 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381 | ||||||||||
| ISSN (online) | 1550-6606 | ||||||||||
| ISSN | 0022-1767 ; 1048-3233 ; 1047-7381 | ||||||||||
| DOI | 10.4049/jimmunol.0803093 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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