Inhibition of the phosphorylation of the regulatory non-structural protein of vesicular stomatitis virus by an antiviral xanthate compound.

The growth of vesicular stomatitis virus (VSV) can be inhibited by the antiviral compound tricyclo-decane-9-yl-xanthogenate (D609). On analysing the antiviral mechanism we found no effect on the primary transcription of infecting VSV genomes. In contrast, the processes of replication and transcription during late stages of infection were inhibited. Despite the synthesis of all five virus-coded proteins (41% to 56% of the uninhibited control), as shown by labelling with [35S]methionine, the phosphorylation of the non-structural (NS) protein was reduced in the presence of the xanthate by a factor of at least 17. The pattern of phosphorylation of the bulk of cellular proteins remained unaltered under the same conditions. A relation between a possible loss of biological activity of the NS protein owing to the lack of phosphorylation and the decreased VSV RNA synthesis is suggested.