Specific amino acid changes in protein 2C, such as Phe to Tyr at residue 164 or Met to Leu at 187 with other mutations, confer guanidine resistance in poliovirus.
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Hypothesis-generating for poliovirus resistance mechanisms; leaves open clinical relevance beyond animal models.
In previous work in our laboratory, 12 guanidine-resistant (gr) mutants of poliovirus were selected from 12 separate stocks of plaque-purified guanidine-sensitive (gs) viruses (K. Anderson-Sillman, S. Bartal, and D. R. Tershak, J. Virol. 50:922-928, 1984). Peptide mapping of protein 2C and evaluation of virus growth at different temperatures enabled us to subdivide these mutants into several distinct groups (D. R. Tershak, Can. J. Microbiol. 31:1166-1168, 1985; Anderson-Sillman et al., J. Virol.). Studies by Pincus et al. indicate that two nucleotide changes in codon 179 of protein 2C leads to an Asn-to-Gly or Asn-to-Ala change and that these missense modifications account for guanidine resistance (S. E. Pincus, H. Rohl, and E. Wimmer, Virology 157:83-88, 1987; S. E. Pincus and E. Wimmer, J. Virol. 60:793-796, 1986). In the present report, we confirm their findings but also show that a single amino acid change of Phe to Tyr in residue 164 of protein 2C or a Met-to-Leu replacement in amino acid 187 coupled with mutations in codons 233 or 295 and 309 could confer guanidine resistance.
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Baltera et al. (1989) studied this question.
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