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

Abstract

This study was conducted to define the effect of micromolar concentrations of A'-tetrahydrocannabinol ( A'-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 [ ''C]glucosamine-labeled infected Vero cells treated with lo-' to lo-' M A'-THC. A drug dose-related depletion of the mature HSV2 major envelope glycoprotein complex ( 1 1 9-kDa average molecular weight), accompanied by accumulation of immature unglycosylated species, was demonstrated by two-dimensional SDS-PAGE in concert with Western immunoblotting or autoradiography. Light and electron microscopy immunoperoxidase staining revealed that A'-THC effected depletion of 119-kDa determinants from the infected cell surface. This depletion occurred concomitantly with accumulation of 1 19-kDa components at the pennucleus. However, the expression of 1 19-kDa glycoproteins on the virion envelope was not affected. These results indicate that A'-THC inhibits the synthesis, maturation, and cellular transport of HSV2specified glycoproteins. Decreased expression of virus glycoproteins on the infected cell surface may affect host immune responsiveness to HSV2.

Immunoregulatory Role of Cannabinoids during Infectious Disease

“…Based on this, Cabral et al [60,61] evaluated the effect of THC on HSV-2 infections. Their studies in vitro, using virus-infected Vero cells pretreated for 24 h with THC, showed a higher extracellular incidence of the virus that correlated with the dissolution of the cellular membrane, and inhibited the synthesis, maturation, and cellular transport of specific HSV-2 glycoproteins [62] and macrovacuoles in the cytoplasm that contained virus aggregates. Their results suggest that treatment with cannabinoids facilitates the exit of the virus from infected cells [63], thereby facilitating viral dispersion.…”

Delta-9 tetrahydrocannabinol (THC) inhibits lytic replication of gamma oncogenic herpesviruses in vitro

“…Early studies have attempted to evaluate whether THC has effects on HSV-1 and HSV-2 replication [37-44]. Most of these studies concluded that THC directly or indirectly enhances replication/reactivation of these viruses, although Lancz et al [42] showed that a very high concentration (330 μM) decreases the infectivity of virions.…”