Rifampicin prevents virosome localization of L65, an essential vaccinia virus polypeptide.
In contrast to its irreversible effect on the Escherichia coliRNA polymerase beta-subunit, the antibiotic rifampicin reversibly inhibits vaccinia virus morphogenesis at a step during the formation of immature viral particles. The protein affected by the presence of rifampicin is L65, a major late vaccinia polypeptide to which mutations that confer rifampicin resistance have been mapped. We now provide evidence using a monospecific anti-L65 serum in concert with immunofluorescence and sucrose gradient analysis that the mechanism of action of rifampicin on vaccinia virus replication involves the inhibition of localization of L65 to the viral factories (virosomes) thereby blocking further development. Studies on the expression and distribution of L65 during the infection cycle reveal that L65 is a stable, nonglycosylated late protein associated with virions. These results are discussed in relationship to the possible in vivo functions of the L65 protein.
Miner
J N
JN
Department of Microbiology, Oregon State University, Corvallis 97331-3804.
Hruby
D E
DE
D015153:Blotting, Western; D002451:Cell Compartmentation; D003001:Cloning, Molecular; D005814:Genes, Viral; D006031:Glycosylation; D008970:Molecular Weight; D009024:Morphogenesis / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012293:Rifampin / Q000494:pharmacology*; D014415:Tunicamycin / Q000494:pharmacology; D014616:Vaccinia virus / Q000187:drug effects* / Q000648:ultrastructure; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D014415:Tunicamycin; D012293:Rifampin