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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)
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.
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.
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.
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.
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