Inhibition of Cell-Associated Herpes Simplex Virus Type 2 Glycoproteins by Δ 9 -Tetrahydrocannabinol

Abstract

This study was conducted to define the effect of micromolar concentrations of Δ⁹-tetrahydrocannabinol (Δ⁹-THC) on the biosynthesis and expression of herpes simplex virus type 2 (HSV2)-specified glycoproteins. Dose-related reductions in all species of virus glycoproteins were recorded by one-dimensional SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography of [¹⁴C]glucosamine-labeled infected Vero cells treated with 10⁻⁷ to 10⁻⁵ M Δ⁹-THC. A drug dose-related depletion of the mature HSV2 major envelope glycoprotein complex (119-kDa average molecular weight), accompanied by accumulation of immature unglycosylated species, was demonstrated by two-dimensional SDS-PAGE in concert with Western immuno-blotting or autoradiography. Light and electron microscopy immunoperoxidase staining revealed that Δ⁹-THC effected depletion of 119-kDa determinants from the infected cell surface. This depletion occurred concomitantly with accumulation of 119-kDa components at the perinucleus. However, the expression of 119-kDa glycoproteins on the virion envelope was not affected. These results indicate that Δ⁹-THC inhibits the synthesis, maturation, and cellular transport of HSV2-specified glycoproteins. Decreased expression of virus glycoproteins on the infected cell surface may affect host immune responsiveness to HSV2.