Effect of snuff extract on the replication and synthesis of viral DNA and proteins in cells infected with herpes simplex virus

Abstract

The water-extractable component of snuff (snuff extract) inhibits the replication of herpes simplex virus (HSV) by suppressing the synthesis of viral DNA. This process probably causes HSV to be oncogenic. To further understand the mechanism of inhibitory action of snuff extract on HSV replication, the effect of snuff extract on the synthesis of viral DNA and proteins in type 1 HSV (HSV-1) infected cells was investigated. Snuff extract inhibited the synthesis of viral DNA and altered the production of certain classes of viral proteins. The syntheses of ICP4, a viral α-protein, and ICP8, a β-protein, were not generally reduced by noncytotoxic concentrations of snuff extract (where ICP = infected cell polypeptide). However, snuff extracts significantly inhibited the production of ICP gC (glycoprotein C), a γ 2-protein, and the inhibition was in a concentration-dependent fashion: the higher the concentration of snuff extracts, the greater the inhibition. Based on the fact that the production of α- and β-proteins is absolutely necessary for and precedes the viral DNA synthesis and that viral γ 2-proteins are mostly produced by the newly synthesized viral DNA, it is concluded that snuff extract inhibits HSV-1 DNA replication directly rather than indirectly via the alteration of viral protein synthesis.