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. 1999 Dec;73(12):10536-9.
doi: 10.1128/JVI.73.12.10536-10539.1999.

Dependence of echovirus 9 on the enterovirus RNA replication inhibitor 2-(alpha-Hydroxybenzyl)-benzimidazole maps to nonstructural protein 2C

D Hadaschik  1 , M Klein, H Zimmermann, H J Eggers, B Nelsen-Salz
Affiliations

Dependence of echovirus 9 on the enterovirus RNA replication inhibitor 2-(alpha-Hydroxybenzyl)-benzimidazole maps to nonstructural protein 2C

D Hadaschik et al. J Virol. 1999 Dec.

Abstract

HBB [2-(alpha-hydroxybenzyl)-benzimidazole] selectively inhibits RNA synthesis of most enteroviruses. However, isolation of HBB-dependent variants is possible. Sequence analysis and characterization of recombinant viruses revealed that HBB dependence maps to the nonstructural protein 2C. A single point mutation at position C(4782)U is sufficient to establish the HBB-dependent phenotype in our echovirus 9 model.

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Figures

FIG. 1
FIG. 1
HBB sensitivity assays of the echovirus 9 strain Barty, the HBB-dependent variant E9H.dep-4, and recombinant viruses. (A) Echovirus 9 Barty MP5 is sensitive to HBB, and the HBB-dependent variant E9H.dep-4 and the recombinant virus rE9-H.dep-f1 exhibit comparable dependence on the antiviral substance. The chimeras exhibit the sensitive (B) or dependent (C) character, comparable to the progenitors in panel A. (D) HBB sensitivity assays of viruses derived from RNA generated by site-directed mutagenesis. The nomenclature is the same as in Fig. 2. The indicated viruses were cultivated in the presence of 0 μM (square), 73 μM (rhomb), 146 μM (triangle), or 220 μM (circle) HBB. The extent of virus-induced cell damage reflecting viral multiplication was estimated by microscopic examination and is given as a percentage. p.i., postinfection.
FIG. 2
FIG. 2
Survey of the genomes of chimeric echovirus 9 Barty strains. Name and position of the mutations of the dependent variant are given in the schematic genome above. Genome fragments derived from the dependent variant are represented by filled bars. Fragments obtained from the sensitive wild-type echovirus 9 are depicted by open bars.
FIG. 3
FIG. 3
Sensitivity assays of the recombinant rE9-H.dep-6 and a guanidine-dependent variant, E9G.dep-12. The indicated viruses were cultivated either in the presence of 73 μM (rhomb), 146 μM (triangle), or 220 μM (circle) HBB or under 1 mM (cross) or 2 mM (star) guanidine. The virus control (square) was grown without an antiviral drug. Results of sensitivity assays of rE9-H.dep-6 in the presence of HBB are given in Fig. 1. The extent of virus-induced cell damage reflecting viral multiplication was estimated by microscopic examination and is given as a percentage. p.i., postinfection.
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References

    1. Argos P, Kamer G, Nicklin M J H, Wimmer E. Similarity in the gene organization and homology between proteins of animal picornaviruses and a plant comovirus suggest common ancestry of these virus families. Nucleic Acids Res. 1984;12:7251–7267. - PMC - PubMed
    1. Baltera R F, Jr, Tershak D R. Guanidine-resistant mutants of poliovirus have distinct mutations in peptide 2C. J Virol. 1989;63:4441–4444. - PMC - PubMed
    1. Barton D J, Flanegan J B. Synchronous replication of poliovirus RNA: initiation of negative-strand RNA synthesis requires the guanidine-inhibited activity of protein 2C. J Virol. 1997;71:8482–8489. - PMC - PubMed
    1. Eggers H J. Benzimidazoles. Selective inhibitors of picornavirus replication in cell culture and in the organism. In: Came P E, Caliguiri L A, editors. Chemotherapy of viral infections. Berlin, Germany: Springer-Verlag; 1982. pp. 377–417.
    1. Eggers H J, Tamm I. Drug dependence of enteroviruses: variants of coxsackie A9 and echo 13 viruses that require 2-(α-hydroxybenzyl)-benzimidazole for growth. Virology. 1963;20:62–74.

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