CYCLOSPORINE-A INHIBITS VACCINIA VIRUS-REPLICATION IN-VITRO

The effect of the immune modulator, Cyclosporin A (CsA) on vaccinia vi rus replication has been examined in cell cultures. In the present stu dy we report that CsA is anti-viral towards vaccinia virus. Viral yiel d was inhibited by more than 97% after 24 h postinfection in the prese nce of 16 mu M to 40 mu M CsA. An analysis of the infectious cycle in greater detail revealed that CsA did not effect the total level of [S- 35] methionine incorporation into vaccinia infected cells. However, bo th early and late viral gene expression were inhibited by CsA. Late vi ral protein synthesis appeared to be more sensitive to the drug. At le ast one late viral polypeptide of approximately Mr 38 000 was virtuall y undetected up to 8 h postinfection in the presence of 40 mu M CsA. H ost protein synthesis which is normally inhibited by the virus was not turned off until very late in infection. Viral DNA replication was al so inhibited by the addition of CsA at levels comparable to those obse rved for late protein synthesis.