title: The early expression of glycoprotein B from herpes simplex virus can be detected by antigen-specific CD8+ T cells.
abstract: The immune response to cutaneous herpes simplex virus type 1 (HSV-1) infection begins with remarkable rapidity. Activation of specific cytotoxic T lymphocytes (CTL) begins within hours of infection, even though the response within the draining lymph nodes peaks nearly 5 days later. HSV gene products are classified into three main groups, alpha, beta, and gamma, based on their kinetics and requirements for expression. In C57BL/6 mice, the immunodominant epitope from HSV is derived from glycoprotein B (gB(498-505)). While gB is considered a gamma or "late" gene product, previous reports have indicated that some level of gene expression may occur soon after infection. Using brefeldin A as a specific inhibitor of viral antigen presentation to major histocompatibility complex class I-restricted CTL, we have formally addressed the timing of gB peptide expression in an immunologically relevant manner following infection. Presentation of gB peptide detected by T-cell activation was first observed within 2 h of infection. Comparison with another viral epitope expressed early during infection, HSV-1 ribonucleotide reductase, demonstrated that gB is presented with the same kinetics as this classical early-gene product. Moreover, this rapidity of gB expression was further illustrated via rapid priming of naïve transgenic CD8(+) T cells in vivo after HSV-1 infection of mice. These results establish that gB is expressed rapidly following HSV-1 infection, at levels capable of effectively stimulating CD8(+) T cells.
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Scott N
authors.initials: SN
authors.lastname: Mueller
authors.forename: Claerwen M
authors.initials: CM
authors.lastname: Jones
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kawaoka
authors.forename: Maria R
authors.initials: MR
authors.lastname: Castrucci
authors.forename: William R
authors.initials: WR
authors.lastname: Heath
authors.forename: Francis R
authors.initials: FR
authors.lastname: Carbone
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006561:Herpes Simplex / Q000276:immunology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010455:Peptides / Q000276:immunology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*
chemical_list: D010455:Peptides; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus