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Journal of Virology, February 2003, p. 2445-2451, Vol. 77, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.4.2445-2451.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Early Expression of Glycoprotein B from Herpes Simplex Virus Can Be Detected by Antigen-Specific CD8+ T Cells

Scott N. Mueller,1,2 Claerwen M. Jones,1 Weisan Chen,3 Yoshihiro Kawaoka,4 Maria R. Castrucci,5 William R. Heath,6* and Francis R. Carbone1*

Department of Microbiology and Immunology, The University of Melbourne,1 Ludwig Institute for Cancer Research, Royal Melbourne Hospital,3 Immunology Division, The Walter and Eliza Hall Institute of Medical Research,Parkville,6 The Cooperative Research Center for Vaccine Technology, Queensland Institute of Medical Research, Royal Brisbane Hospital, Herston, Australia,2 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin—Madison, Madison, Wisconsin,4 Istituto Superiore di Sanita, Rome, Italy5

Received 16 September 2002/ Accepted 6 November 2002

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}, ß, and {gamma}, based on their kinetics and requirements for expression. In C57BL/6 mice, the immunodominant epitope from HSV is derived from glycoprotein B (gB498-505). 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.


* Corresponding author. Mailing address for Francis R. Carbone: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia. Phone: 61-3-8344-9923. Fax: 61-3-9347-1540. E-mail: fcarbone{at}unimelb.edu.au. Mailing address for William R. Heath: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia. Phone: 61-3-9345-2482. Fax: 61-3-9347-0852. E-mail: heath@wehi.edu.au.


Journal of Virology, February 2003, p. 2445-2451, Vol. 77, No. 4
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.4.2445-2451.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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Copyright © 2003 by the American Society for Microbiology. All rights reserved.