Dehydroepiandrosterone and
androstenediol (AED) have previously been found to protect mice from viral-induced
encephalitis resulting in an increased survival rate of the animals. These
hormones have been shown to antagonize
corticosteroids, which have immunosuppressive effects in vivo and in vitro, suggesting the
antiviral effect of
DHEA and AED may be linked to the anticorticosteroid action. The present study was undertaken to address the immune response to herpes simplex virus type 1 (HSV-1) during the acute
ocular infection with and without AED treatment focusing on the early immune events in the eye and trigeminal ganglion. AED treatment was found to significantly improve the survival of HSV-1-infected mice in a dose-dependent fashion. While AED did not antagonize the elevated serum
corticosterone levels following acute
infection, AED enhanced the expression of IFN-alpha
mRNA and decreased the expression of HSV-1-infected cell
polypeptide 27
mRNA in the trigeminal ganglion during the acute (day 6 postinfection)
infection of mice, as determined by reverse transcription-PCR. However, there was no change in the viral load from the eye or trigeminal ganglion when comparing the AED-treated with the vehicle-treated mice. Neutralization Abs to IFN-alpha, -beta, or -alpha/beta, but not control Ab, blocked the protective effect following AED exposure, confirming the involvement of type I IFN in the enhancement of survival in AED-treated mice. Collectively, these results identify innate immunity as a key component in augmenting the survival of HSV-1-infected mice following AED treatment.