| 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
|
| リソース情報 |
| ヒト・動物細胞 |
MRC-5 |
