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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.
Insights
Rifamycin derivatives disrupt poxvirus assembly by affecting viral morphogenesis. This antiviral effect is linked to the macrocyclic ring structure, not the side chain, with some derivatives also showing cytotoxicity.
Area of Science:
- Virology
- Microbiology
- Cell Biology
Background:
- Poxvirus assembly involves complex morphogenesis.
- Rifampin has been shown to interrupt poxvirus assembly.
- Rifamycin derivatives are a class of antibiotics with potential antiviral properties.
Purpose of the Study:
- To investigate the effect of rifamycin derivatives on vaccinia virus morphogenesis.
- To determine the specific structural components of rifampin responsible for its antiviral activity.
- To assess the cytotoxicity of rifamycin derivatives.
Main Methods:
- Electron microscopy was used to observe viral structures in infected cells.
- HeLa cells infected with vaccinia virus were treated with various rifamycin derivatives.
- A rifampin-resistant vaccinia mutant was utilized to assess drug resistance.
Main Results:
- Membrane-limited structures, resembling virus envelope precursors, were observed in treated cells.
- The antiviral effect was associated with the macrocyclic ring of rifampin, not the hydrazone side chain.
- A rifampin-resistant mutant was cross-resistant to the effects of other derivatives on morphogenesis.
- 3-formyl rifamycin SV and AF/DMI exhibited significant cytotoxicity.
Conclusions:
- The antiviral effect of rifampin derivatives on vaccinia virus assembly is specific and mediated by the macrocyclic ring.
- Structural modifications to the rifampin side chain do not abolish the antiviral effect.
- Certain rifamycin derivatives possess cytotoxic properties beyond their impact on viral morphogenesis.