論文 - 詳細
| RRC ID | 44589 |
|---|---|
| 著者 | Imai T, Koyanagi N, Ogawa R, Shindo K, Suenaga T, Sato A, Arii J, Kato A, Kiyono H, Arase H, Kawaguchi Y. |
| タイトル | Us3 kinase encoded by herpes simplex virus 1 mediates downregulation of cell surface major histocompatibility complex class I and evasion of CD8+ T cells. |
| ジャーナル | PLoS One |
| Abstract |
Detection and elimination of virus-infected cells by CD8(+) cytotoxic T lymphocytes (CTLs) depends on recognition of virus-derived peptides presented by major histocompatibility complex class I (MHC-I) molecules on the surface of infected cells. In the present study, we showed that inactivation of the activity of viral kinase Us3 encoded by herpes simplex virus 1 (HSV-1), the etiologic agent of several human diseases and a member of the alphaherpesvirinae, significantly increased cell surface expression of MHC-I, thereby augmenting CTL recognition of infected cells in vitro. Overexpression of Us3 by itself had no effect on cell surface expression of MHC-I and Us3 was not able to phosphorylate MHC-I in vitro, suggesting that Us3 indirectly downregulated cell surface expression of MHC-I in infected cells. We also showed that inactivation of Us3 kinase activity induced significantly more HSV-1-specific CD8(+) T cells in mice. Interestingly, depletion of CD8(+) T cells in mice significantly increased replication of a recombinant virus encoding a kinase-dead mutant of Us3, but had no effect on replication of a recombinant virus in which the kinase-dead mutation was repaired. These results indicated that Us3 kinase activity is required for efficient downregulation of cell surface expression of MHC-I and mediates evasion of HSV-1-specific CD8(+) T cells. Our results also raised the possibility that evasion of HSV-1-specific CD8(+) T cells by HSV-1 Us3-mediated inhibition of MHC-I antigen presentation might in part contribute to viral replication in vivo. |
| 巻・号 | 8(8) |
| ページ | e72050 |
| 公開日 | 2013-1-1 |
| DOI | 10.1371/journal.pone.0072050 |
| PII | PONE-D-13-19194 |
| PMID | 23951282 |
| PMC | PMC3741198 |
| MeSH | Animals Antigen Presentation / immunology Antigens, Viral / immunology CD8-Positive T-Lymphocytes / immunology CD8-Positive T-Lymphocytes / metabolism* CD8-Positive T-Lymphocytes / virology* Cell Line Cell Membrane / metabolism Chlorocebus aethiops Enzyme Activation Female Gene Order Genome, Viral Herpesvirus 1, Human / genetics Herpesvirus 1, Human / immunology Herpesvirus 1, Human / metabolism* Histocompatibility Antigens Class I / genetics Histocompatibility Antigens Class I / immunology Histocompatibility Antigens Class I / metabolism* Humans Killer Cells, Natural / immunology Lymphocyte Depletion Mice Mutation Phosphorylation Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* T-Lymphocytes, Cytotoxic / immunology Vero Cells Viral Proteins / genetics Viral Proteins / metabolism* Virus Replication / genetics Virus Replication / immunology |
| IF | 2.74 |
| 引用数 | 24 |
| WOS 分野 | VIROLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MRC-5 |