May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Female Sex Hormones Inhibit the Function of HSV-Specific CD8+ T Cells in Latently Infected Trigeminal Ganglia and Induce HSV-1 Reactivation From Latency
Author Affiliations & Notes
  • R. L. Hendricks
    Ophthalmology, Immunology, and Molecular Genetics and Biochemistry, Univ of Pittsburgh Eye & Ear Inst, Pittsburgh, Pennsylvania
  • J. L. Busch
    OBGYN and Reproductive Sciences, Univ of Pittsburgh, Pittsburgh, Pennsylvania
  • T. L. Cherpes
    OBGYN and Reproductive Sciences, Univ of Pittsburgh, Pittsburgh, Pennsylvania
  • Footnotes
    Commercial Relationships  R.L. Hendricks, None; J.L. Busch, None; T.L. Cherpes, None.
  • Footnotes
    Support  NIH grants: EY09545, EY10359, EY P30EY008098, K23 AI064396; and by non-restricted grants from Research to Prevent Blindness, New York, NY, and the Eye and Ear Foundation of Pittsburgh
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2828. doi:https://doi.org/
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      R. L. Hendricks, J. L. Busch, T. L. Cherpes; Female Sex Hormones Inhibit the Function of HSV-Specific CD8+ T Cells in Latently Infected Trigeminal Ganglia and Induce HSV-1 Reactivation From Latency. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2828. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : The existing literature supports the following contentions: i) that oral and injectable hormonal contraceptives are risk factors for HSV shedding in the female genital tract; ii) that HSV shedding results from viral reactivation from latency in sensory neurons; iii) that CD8+ T cells inhibit HSV-1 reactivation from latency; and iv) that estrogen and progesterone inhibit T cell function. Based on these observations we hypothesized that estrogen and progesterone could induce HSV-1 reactivation from latency in the trigeminal ganglion (TG) at least in part by inhibiting the capacity of TG-resident CD8+ T cells to block HSV-1 reactivation from latency in sensory neurons.

Methods: : ovariectomized mice received time-release pellets containing 17-β estradiol (E) or medroxyprogesterone acetate (MPA) during viral latency and the function of TG-resident CD8+ T cells was measured directly ex vivo and HSV-1 reactivation was monitored by quantifying viral genome copy number. Alternatively, ex vivo cultures of latently infected TG were treated with E or MPA and CD8+ T cell function and reactivation frequency were measured.

Results: : MPA dramatically inhibited CD8+ T cell function in vivo and in vitro and induced HSV-1 reactivation from latency both by inhibiting CD8+ T cell function and by a leukocyte-independent mechanism. E did not significantly influence CD8+ T cell function, but also induced HSV-1 reactivation from latency by a leukocyte-independent mechanism.

Conclusions: : use of estrogen and progesterone as oral contraceptives could increase HSV shedding into the female genital tract by inhibiting the capacity of CD8+ T cells to block viral reactivation and by directly inducing reactivation in sensory neurons. Investigation of the effect of oral contraceptives on HSV-1 shedding at the cornea and on susceptibility to recurrent herpetic keratitis is warranted.

Keywords: herpes simplex virus • immunomodulation/immunoregulation • cytokines/chemokines 
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