RRC ID 44589
Author Imai T, Koyanagi N, Ogawa R, Shindo K, Suenaga T, Sato A, Arii J, Kato A, Kiyono H, Arase H, Kawaguchi Y.
Title Us3 kinase encoded by herpes simplex virus 1 mediates downregulation of cell surface major histocompatibility complex class I and evasion of CD8+ T cells.
Journal 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.
Volume 8(8)
Pages e72050
Published 2013
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 2.776
Times Cited 24
Human and Animal Cells