Androstenediol antagonizes herpes simplex virus type 1-induced encephalitis through the augmentation of type I IFN production.

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.