Increased frequency of virus shedding by herpes simplex virus 2-infected Guinea pigs in the absence of CD4 T lymphocytes

Nigel Bourne, Clarice L. Perry, Brianne N. Banasik, Aaron L. Miller, Mellodee White, Richard Pyles, Hubert Schäfer, Gregg Milligan

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Reactivation of herpes simplex virus 2 (HSV-2) results in infection of epithelial cells at the neuro-epithelial junction and shedding of virus at the epithelial surface. Virus shedding can occur in either the presence or absence of clinical disease and is usually of short duration, although the shedding frequency varies among individuals. The basis for host control of virus shedding is not well understood, although adaptive immune mechanisms are thought to play a central role. To determine the importance of CD4 T cells in control of HSV-2 shedding, this subset of immune cells was depleted from HSV-2-infected Guinea pigs by injection of an anti-CD4 monoclonal antibody (MAb). Guinea pigs were treated with the depleting MAb after establishment of a latent infection, and vaginal swabs were taken daily to monitor shedding by quantitative PCR. The cumulative number of HSV-2 shedding days and the mean number of days virus was shed were significantly increased in CD4-depleted compared to control-treated animals. However, there was no difference in the incidence of recurrent disease between the two treatment groups. Serum antibody levels and the number of HSV-specific antibody-secreting cells in secondary lymphoid tissues were unaffected by depletion of CD4 T cells; however, the frequency of functional HSV-specific, CD8 gamma interferon-secreting cells was significantly decreased. Together, these results demonstrate an important role for CD4 T lymphocytes in control of virus shedding that may be mediated in part by maintenance of HSV-specific CD8 T cell populations. These results have important implications for development of therapeutic vaccines designed to control HSV-2 shedding.

Original languageEnglish (US)
Article numbere0172118
JournalJournal of Virology
Volume93
Issue number4
DOIs
StatePublished - Feb 1 2019

Fingerprint

Human herpesvirus 2
Virus Shedding
viral shedding
Human Herpesvirus 2
guinea pigs
Guinea Pigs
T-lymphocytes
T-Lymphocytes
monoclonal antibodies
antibodies
cells
Monoclonal Antibodies
interferon-gamma
infection
Antibody-Producing Cells
quantitative polymerase chain reaction
epithelial cells
Lymphoid Tissue
Infection
vaccines

Keywords

  • CD4 T lymphocyte
  • Genital mucosa
  • Guinea pig
  • HSV-2
  • HSV-2 shedding

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Increased frequency of virus shedding by herpes simplex virus 2-infected Guinea pigs in the absence of CD4 T lymphocytes. / Bourne, Nigel; Perry, Clarice L.; Banasik, Brianne N.; Miller, Aaron L.; White, Mellodee; Pyles, Richard; Schäfer, Hubert; Milligan, Gregg.

In: Journal of Virology, Vol. 93, No. 4, e0172118, 01.02.2019.

Research output: Contribution to journalArticle

Bourne, Nigel ; Perry, Clarice L. ; Banasik, Brianne N. ; Miller, Aaron L. ; White, Mellodee ; Pyles, Richard ; Schäfer, Hubert ; Milligan, Gregg. / Increased frequency of virus shedding by herpes simplex virus 2-infected Guinea pigs in the absence of CD4 T lymphocytes. In: Journal of Virology. 2019 ; Vol. 93, No. 4.
@article{ebb645c715014de8ae946584cf6fbc0d,
title = "Increased frequency of virus shedding by herpes simplex virus 2-infected Guinea pigs in the absence of CD4 T lymphocytes",
abstract = "Reactivation of herpes simplex virus 2 (HSV-2) results in infection of epithelial cells at the neuro-epithelial junction and shedding of virus at the epithelial surface. Virus shedding can occur in either the presence or absence of clinical disease and is usually of short duration, although the shedding frequency varies among individuals. The basis for host control of virus shedding is not well understood, although adaptive immune mechanisms are thought to play a central role. To determine the importance of CD4 T cells in control of HSV-2 shedding, this subset of immune cells was depleted from HSV-2-infected Guinea pigs by injection of an anti-CD4 monoclonal antibody (MAb). Guinea pigs were treated with the depleting MAb after establishment of a latent infection, and vaginal swabs were taken daily to monitor shedding by quantitative PCR. The cumulative number of HSV-2 shedding days and the mean number of days virus was shed were significantly increased in CD4-depleted compared to control-treated animals. However, there was no difference in the incidence of recurrent disease between the two treatment groups. Serum antibody levels and the number of HSV-specific antibody-secreting cells in secondary lymphoid tissues were unaffected by depletion of CD4 T cells; however, the frequency of functional HSV-specific, CD8 gamma interferon-secreting cells was significantly decreased. Together, these results demonstrate an important role for CD4 T lymphocytes in control of virus shedding that may be mediated in part by maintenance of HSV-specific CD8 T cell populations. These results have important implications for development of therapeutic vaccines designed to control HSV-2 shedding.",
keywords = "CD4 T lymphocyte, Genital mucosa, Guinea pig, HSV-2, HSV-2 shedding",
author = "Nigel Bourne and Perry, {Clarice L.} and Banasik, {Brianne N.} and Miller, {Aaron L.} and Mellodee White and Richard Pyles and Hubert Sch{\"a}fer and Gregg Milligan",
year = "2019",
month = "2",
day = "1",
doi = "10.1128/JVI.01721-18",
language = "English (US)",
volume = "93",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "4",

}

TY - JOUR

T1 - Increased frequency of virus shedding by herpes simplex virus 2-infected Guinea pigs in the absence of CD4 T lymphocytes

AU - Bourne, Nigel

AU - Perry, Clarice L.

AU - Banasik, Brianne N.

AU - Miller, Aaron L.

AU - White, Mellodee

AU - Pyles, Richard

AU - Schäfer, Hubert

AU - Milligan, Gregg

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Reactivation of herpes simplex virus 2 (HSV-2) results in infection of epithelial cells at the neuro-epithelial junction and shedding of virus at the epithelial surface. Virus shedding can occur in either the presence or absence of clinical disease and is usually of short duration, although the shedding frequency varies among individuals. The basis for host control of virus shedding is not well understood, although adaptive immune mechanisms are thought to play a central role. To determine the importance of CD4 T cells in control of HSV-2 shedding, this subset of immune cells was depleted from HSV-2-infected Guinea pigs by injection of an anti-CD4 monoclonal antibody (MAb). Guinea pigs were treated with the depleting MAb after establishment of a latent infection, and vaginal swabs were taken daily to monitor shedding by quantitative PCR. The cumulative number of HSV-2 shedding days and the mean number of days virus was shed were significantly increased in CD4-depleted compared to control-treated animals. However, there was no difference in the incidence of recurrent disease between the two treatment groups. Serum antibody levels and the number of HSV-specific antibody-secreting cells in secondary lymphoid tissues were unaffected by depletion of CD4 T cells; however, the frequency of functional HSV-specific, CD8 gamma interferon-secreting cells was significantly decreased. Together, these results demonstrate an important role for CD4 T lymphocytes in control of virus shedding that may be mediated in part by maintenance of HSV-specific CD8 T cell populations. These results have important implications for development of therapeutic vaccines designed to control HSV-2 shedding.

AB - Reactivation of herpes simplex virus 2 (HSV-2) results in infection of epithelial cells at the neuro-epithelial junction and shedding of virus at the epithelial surface. Virus shedding can occur in either the presence or absence of clinical disease and is usually of short duration, although the shedding frequency varies among individuals. The basis for host control of virus shedding is not well understood, although adaptive immune mechanisms are thought to play a central role. To determine the importance of CD4 T cells in control of HSV-2 shedding, this subset of immune cells was depleted from HSV-2-infected Guinea pigs by injection of an anti-CD4 monoclonal antibody (MAb). Guinea pigs were treated with the depleting MAb after establishment of a latent infection, and vaginal swabs were taken daily to monitor shedding by quantitative PCR. The cumulative number of HSV-2 shedding days and the mean number of days virus was shed were significantly increased in CD4-depleted compared to control-treated animals. However, there was no difference in the incidence of recurrent disease between the two treatment groups. Serum antibody levels and the number of HSV-specific antibody-secreting cells in secondary lymphoid tissues were unaffected by depletion of CD4 T cells; however, the frequency of functional HSV-specific, CD8 gamma interferon-secreting cells was significantly decreased. Together, these results demonstrate an important role for CD4 T lymphocytes in control of virus shedding that may be mediated in part by maintenance of HSV-specific CD8 T cell populations. These results have important implications for development of therapeutic vaccines designed to control HSV-2 shedding.

KW - CD4 T lymphocyte

KW - Genital mucosa

KW - Guinea pig

KW - HSV-2

KW - HSV-2 shedding

UR - http://www.scopus.com/inward/record.url?scp=85061143236&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061143236&partnerID=8YFLogxK

U2 - 10.1128/JVI.01721-18

DO - 10.1128/JVI.01721-18

M3 - Article

VL - 93

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 4

M1 - e0172118

ER -