NOVOBIOCIN INHIBITS VACCINIA VIRUS-REPLICATION BY BLOCKING VIRUS ASSEMBLY

Novobiocin inhibits the replication of vaccinia virus in cultured BSC4 0 cells. All classes of viral proteins were synthesized during synchro nous infection in the presence of drug. The onset of DNA replication w as delayed slightly, yet the extent of DNA replication in the presence of novobiocin was comparable to that of a control infection. A delay in the temporal transition to late viral protein synthesis was in keep ing with the effects on DNA replication. Although the precursor forms of the major viral structural proteins were synthesized normally at la te times, the proteolytic processing of these polypeptides was inhibit ed, which suggested an impediment to virus assembly. Electron microsco py revealed that novobiocin blocked virus morphogenesis at an early st age. Conversion of the concatameric DNA replication intermediates into hairpin telomeres occurred in the presence of novobiocin, confirming that telomere resolution was not coupled to virus assembly. Novobiocin is the latest addition to a class of antipoxviral agents, which inclu des rifampin and IMCBH, that arrest morphogenesis. (C) 1997 Academic P ress.