A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes.
Herpes simplex virus (HSV) infection of human fibroblasts rapidly renders the cells resistant to lysis by HSV-specific CD8+ cytotoxic T lymphocytes (CTLs), which normally recognize cell surface major histocompatibility complex (MHC) class I proteins presenting viral peptides. Within 3 hr of infection with HSV, MHC class I protein complexes are retained in the endoplasmic reticulum (ER)/cis Golgi and show properties of complexes lacking antigenic peptide. The HSV immediate-early protein ICP47 is both necessary and sufficient to block transport of class I proteins and to inhibit lysis by CD8+ CTLs. The target for ICP47 is not known, but since ICP47 does not associate with membranes, it appears that ICP47 inhibits the production or stabilization of antigenic peptides or their translocation into the ER/cis Golgi. Thus, by expressing ICP47, HSV can evade detection by CD8+ T lymphocytes, perhaps explaining the predominance of CD4+ rather than CD8+ HSV-specific CTLs in vivo.
York
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IA
Department of Pathology, McMaster University Hamilton, Ontario, Canada.
Roop
C
C
Andrews
D W
DW
Riddell
S R
SR
Graham
F L
FL
Johnson
D C
DC
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology / Q000382:microbiology; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D017510:Protein Folding; D011994:Recombinant Proteins; D018139:Simplexvirus / Q000276:immunology / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000235:genetics
D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin