A mutant of Sindbis virus that is resistant to pyrazofurin encodes an altered RNA polymerase.

@article{Lin2000AMO,
  title={A mutant of Sindbis virus that is resistant to pyrazofurin encodes an altered RNA polymerase.},
  author={Y. H. Lin and Pooja Yadav and Roald Ravatn and Victor Stollar},
  journal={Virology},
  year={2000},
  volume={272 1},
  pages={
          61-71
        }
}
Pyrazofurin (PZF), a cytidine analog and an inhibitor of orotate monophosphate decarboxylase, has been shown to decrease the levels of UTP and CTP in treated cells. When Sindbis virus (SV)-infected Aedes albopictus cells were treated with PZF, the yield of virus was reduced 100- to 1000-fold. By serial passage of our standard SV(STD) in Ae. albopictus cells in the presence of increasing concentrations of PZF, a mutant, SV(PZF), was derived, which was not inhibited by PZF. SV(PZF) is also… 
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It was observed that the SVpzf mutations enhance the in vitro synthesis of SGRNA at the lowest concentrations of UTP/CTP and that the single SVcpc mutation enhances the synthesis of G RNA at the highest concentrations of CTP tested.
Evolution of Sindbis Virus with a Low-Methionine-Resistant Phenotype Is Dependent Both on a Pre-Existing Mutation and on the Methionine Concentration in the Medium
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The experiments highlight how a virus population by mutation and selection can adapt to the intracellular concentration of a simple metabolite, S-adenosylmethionine, and indicate that in these mixed infection the presence of SVwt inhibited the emergence of SVlm21.
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The new proposition is that ribavirin, when converted to the triphosphate, is utilized by the viral RNA-dependent RNA polymerase and causes lethal mutagenesis of the viral genome.
A cell-free system for the synthesis of Sindbis virus subgenomic RNA: importance of the concentration of the initiating NTP.
Identification of the amino acid sequence in Sindbis virus nsP4 that binds to the promoter for the synthesis of the subgenomic RNA.
  • Mei-Ling Li, V. Stollar
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2004
TLDR
A gel mobility-shift assay was used to demonstrate the binding of the Sindbis virus transcriptase to the promoter for the synthesis of subgenomic (SG) RNA and demonstrated that only the Arg residues at positions 331 and 332 were required for binding nsP4 to the SG promoter.
Functions of alphavirus nonstructural proteins in RNA replication
Alphavirus Minus-Strand RNA Synthesis: Identification of a Role for Arg183 of the nsP4 Polymerase
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It is concluded that Arg183 within the Pro180-Asn-Ile-Arg-Ser184 sequence of the SIN nsP4 polymerase contributes to the efficient initiation of minus strands or the formation of its replicase and that a host factor participates in this event.
Molecular Determinants of Substrate Specificity for Semliki Forest Virus Nonstructural Protease
ABSTRACT The C-terminal cysteine protease domain of Semliki Forest virus nonstructural protein 2 (nsP2) regulates the virus life cycle by sequentially cleaving at three specific sites within the…
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