ANDROSTENEDIOL ANTAGONIZES HERPES-SIMPLEX VIRUS TYPE 1-INDUCED ENCEPHALITIS THROUGH THE AUGMENTATION OF TYPE-I IFN PRODUCTION

Dehydroepiandrosterone and androstenediol (AED) have previously been f ound to protect mice from viral-induced encephalitis resulting in an i ncreased 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 ma y be Linked to the anticorticosteroid action, The present study was un dertaken to address the immune response to herpes simplex virus type 1 (HSV-1) during the acute ocular infection with and without AED treatm ent focusing on the early immune events in the eye and trigeminal gang lion, AED treatment was found to significantly improve the survival of HSV-1-infected mice in a dose-dependent fashion, While AED did not an tagonize the elevated serum corticosterone levels following acute infe ction, AED enhanced the expression of IFN-alpha mRNA and decreased the expression of HSV-1-infected cell polypeptide 27 mRNA in the trigemin al ganglion during; the acute (day 6 postinfection) infection of mice, as determined by reverse transcription-PCR, However, there was no cha nge in the viral load from the eye or trigeminal ganglion when compari ng the AED-treated with the vehicle-treated mice. Neutralization Abs t o IFN-alpha -beta, or -alpha/beta, but not control Ab, blocked the pro tective effect following AED exposure, confirming the involvement of t ype I IFN in the enhancement of survival in AED-treated mice, Collecti vely, these results identify innate immunity as a key component in aug menting the survival of HSV-1-infected mice following AED treatment.