Inhibition by indomethacin of in vitro reactivation of latent herpes simplex virus type 1 in murine trigeminal ganglia

Abstract

Infectious virus could no longer be detected in the trigeminal ganglia removed from mice 25 days after infection with herpes simplex virus type 1 (HSV-1) by the lip route. When the ganglia were cultured in vitro for 1 or 2 days, infectious HSV-1 was again detected in the ganglia, indicating the reactivation of latent HSV-1. The effect of indomethacin on this reactivation was examined. When the ganglia were cultivated in the presence of 5 X 10(-4) M-indomethacin, the appearance of infectious virus in the ganglia was almost completely inhibited. After removal of indomethacin, infectious virus appeared and the virus titre reached levels found in the ganglia cultured in indomethacin-free medium, indicating that the inhibition of the reactivation may not be due to the cytotoxic effect of indomethacin on the ganglionic cells. The inhibitory effect of indomethacin was only seen when it was added shortly after explantation. These results suggest that indomethacin affects some early processes of viral reactivation in the explanted ganglia. The synthesis of prostaglandins (PGE and PGB) found in the explanted ganglia was strongly suppressed by indomethacin, as was the viral reactivation. Other inhibitors of prostaglandin synthesis, i.e. tetracaine, mepacrine and mefenamic acid, also inhibited viral reactivation in the explanted ganglia. These results suggest that the inhibitory effect of indomethacin on the reactivation of latent HSV-1 may be due to the inhibition of prostaglandin synthesis, although it is possible that other cellular changes which could be caused by indomethacin contributed to the suppression of reactivation.