Similar Effect of Rifampin and Other Rifamycin Derivatives on Vaccinia Virus Morphogenesis

Abstract

Membrane-limited structures, resembling virus envelope precursors previously shown to form during the interruption of poxvirus assembly by rifampin, were now observed by electron microscopy in vaccinia-infected HeLa cells treated with a series of rifamycin derivatives. The active compounds N -demethyl rifampin, AF/DMI, and 3-formyl rifamycin SV lacked, respectively, a methyl group, the piperazine ring, and the hydrazone portion of rifampin. A vaccinia mutant selected only for resistance to rifampin was also resistant to the effect on morphogenesis produced by all of the rifamycin derivatives. We concluded that this antiviral effect was specific and was a property associated with the macrocyclic ring rather than the hydrazone-containing side chain of rifampin. In addition to their effects on vaccinia morphogenesis, 3-formyl rifamycin SV and AF/DMI had unusual cytotoxic effects.