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