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Published online ahead of print on 4 March 2009 as doi:10.1099/vir.0.008771-0
Journal of General Virology 2009;90:1153.

A more recent version of this article appeared on May 1, 2009 J Gen Virol (2009), DOI 10.1099/vir.0.008771-0
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Herpes simplex virus type 2 tegument proteins contain subdominant T-cell epitopes detectable in BALB/c mice after DNA immunization and infection

William J Muller1,5, Lichun Dong2, Adrian Vilalta3, Benjamin Byrd2, Kai M Wilhelm2, Christopher L McClurkan2, Michal Margalith3, Chao Liu2, David Kaslow3, John Sidney4, Alessandro Sette4 and David M Koelle2

1 Northwestern University;
2 University of Washington;
3 Vical, Inc., San Diego, CA;
4 La Jolla Institute for Allergy and Immunology, La Jolla, CA

5 E-mail: wjmuller{at}northwestern.edu

Cytotoxic T-cells are important in controlling herpes simplex virus type 2 (HSV-2) reactivation and peripheral lesion resolution. Humans latently infected with HSV-2 have cytotoxic T-cells directed against epitopes present in tegument proteins. Studies in mice of immunity to HSV have commonly focused on immunodominant responses in HSV envelope glycoproteins. These antigens have not proved to be an effective prophylactic vaccine target for most of the human population. The murine immune response against HSV tegument proteins has not been explored. We analyzed cellular responses in BALB/c mice directed against the tegument proteins encoded by UL46, UL47, and UL49 and against the envelope glycoprotein gD after DNA vaccination or HSV-2 infection. Splenocyte T-cell responses to overlapping peptides from UL46 and UL47 were more than 500 interferon-{gamma} spot forming units per 106 responder cells after DNA vaccination. Peptide truncation studies, responder cell fractionation, and major histocompatibility complex binding studies identified several CD8+ and CD4+ epitopes. Cellular responses to tegument protein epitopes were also detected after HSV-2 infection. Tegument proteins are rational candidates for further HSV-2 vaccine research.

Received 11 November 2008; accepted 8 January 2009.




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