Herpes simplex virus type 2 tegument proteins contain subdominant T-cell epitopes detectable in BALB/c mice after DNA immunization and infection

Wiliam J. Muller*, Lichun Dong, Adrian Vilalta, Benjamin Byrd, Kai M. Wilhelm, Christopher L. McClurkan, Michal Margalith, Chao Liu, David Kaslow, John Sidney, Alessandro Sette, David M. Koelle

*Corresponding author for this work

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 analysed 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. After DNA vaccination, the splenocyte T-cell response to overlapping peptides from UL46 and UL47 was more than 500 gamma interferon spot-forming units per 106 responder cells. 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.

Original languageEnglish (US)
Pages (from-to)1153-1163
Number of pages11
JournalJournal of General Virology
Volume90
Issue number5
DOIs
StatePublished - Jun 29 2009

Fingerprint

T-Lymphocyte Epitopes
Human Herpesvirus 2
Immunization
DNA
Epitopes
Infection
Virus Diseases
Proteins
T-Lymphocytes
Herpes Simplex Virus Vaccines
Glycoproteins
Vaccination
Cell Fractionation
Peptides
Major Histocompatibility Complex
Interferon-gamma
Immunity
Vaccines
Antigens
Research

ASJC Scopus subject areas

  • Virology

Cite this

Muller, Wiliam J. ; Dong, Lichun ; Vilalta, Adrian ; Byrd, Benjamin ; Wilhelm, Kai M. ; McClurkan, Christopher L. ; Margalith, Michal ; Liu, Chao ; Kaslow, David ; Sidney, John ; Sette, Alessandro ; Koelle, David M. / Herpes simplex virus type 2 tegument proteins contain subdominant T-cell epitopes detectable in BALB/c mice after DNA immunization and infection. In: Journal of General Virology. 2009 ; Vol. 90, No. 5. pp. 1153-1163.
@article{ff810ad2f2f64fc3a9721850a3630f1e,
title = "Herpes simplex virus type 2 tegument proteins contain subdominant T-cell epitopes detectable in BALB/c mice after DNA immunization and infection",
abstract = "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 analysed 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. After DNA vaccination, the splenocyte T-cell response to overlapping peptides from UL46 and UL47 was more than 500 gamma interferon spot-forming units per 106 responder cells. 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.",
author = "Muller, {Wiliam J.} and Lichun Dong and Adrian Vilalta and Benjamin Byrd and Wilhelm, {Kai M.} and McClurkan, {Christopher L.} and Michal Margalith and Chao Liu and David Kaslow and John Sidney and Alessandro Sette and Koelle, {David M.}",
year = "2009",
month = "6",
day = "29",
doi = "10.1099/vir.0.008771-0",
language = "English (US)",
volume = "90",
pages = "1153--1163",
journal = "Journal of General Virology",
issn = "0022-1317",
publisher = "Society for General Microbiology",
number = "5",

}

Muller, WJ, Dong, L, Vilalta, A, Byrd, B, Wilhelm, KM, McClurkan, CL, Margalith, M, Liu, C, Kaslow, D, Sidney, J, Sette, A & Koelle, DM 2009, 'Herpes simplex virus type 2 tegument proteins contain subdominant T-cell epitopes detectable in BALB/c mice after DNA immunization and infection', Journal of General Virology, vol. 90, no. 5, pp. 1153-1163. https://doi.org/10.1099/vir.0.008771-0

Herpes simplex virus type 2 tegument proteins contain subdominant T-cell epitopes detectable in BALB/c mice after DNA immunization and infection. / Muller, Wiliam J.; Dong, Lichun; Vilalta, Adrian; Byrd, Benjamin; Wilhelm, Kai M.; McClurkan, Christopher L.; Margalith, Michal; Liu, Chao; Kaslow, David; Sidney, John; Sette, Alessandro; Koelle, David M.

In: Journal of General Virology, Vol. 90, No. 5, 29.06.2009, p. 1153-1163.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Herpes simplex virus type 2 tegument proteins contain subdominant T-cell epitopes detectable in BALB/c mice after DNA immunization and infection

AU - Muller, Wiliam J.

AU - Dong, Lichun

AU - Vilalta, Adrian

AU - Byrd, Benjamin

AU - Wilhelm, Kai M.

AU - McClurkan, Christopher L.

AU - Margalith, Michal

AU - Liu, Chao

AU - Kaslow, David

AU - Sidney, John

AU - Sette, Alessandro

AU - Koelle, David M.

PY - 2009/6/29

Y1 - 2009/6/29

N2 - 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 analysed 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. After DNA vaccination, the splenocyte T-cell response to overlapping peptides from UL46 and UL47 was more than 500 gamma interferon spot-forming units per 106 responder cells. 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.

AB - 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 analysed 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. After DNA vaccination, the splenocyte T-cell response to overlapping peptides from UL46 and UL47 was more than 500 gamma interferon spot-forming units per 106 responder cells. 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.

UR - http://www.scopus.com/inward/record.url?scp=67449104508&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67449104508&partnerID=8YFLogxK

U2 - 10.1099/vir.0.008771-0

DO - 10.1099/vir.0.008771-0

M3 - Article

VL - 90

SP - 1153

EP - 1163

JO - Journal of General Virology

JF - Journal of General Virology

SN - 0022-1317

IS - 5

ER -