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PMID: 3003395 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

Guanidine-selected mutants of poliovirus: mapping of point mutations to polypeptide 2C.

Journal of virology ·Vol. 57 ·No. 2 ·1986-02-00 ·Pages 638-46

Pincus SE, Diamond DC, Emini EA, Wimmer E

Abstract

Sequence analysis of the genomic RNA of interstrain guanidine-resistant and antibody-resistant variant recombinants of poliovirus type 1 mapped the resistance of mutants capable of growth in 2.0 mM guanidine hydrochloride to a region located 3' of nucleotide 4444. This region of the viral genome specifies the nonstructural protein 2C. The sequence of genomic RNA encoding 2C from six independently isolated mutants resistant to 2.0 mM guanidine was determined. All six isolates contained a mutation in 2C at the same position in all cases, resulting in two types of amino acid changes. Dependent mutants were examined and found to contain two amino acid changes each within 2C. Mutants resistant to 0.53 mM guanidine were isolated and found to lack the mutations seen in variants resistant to 2.0 mM guanidine. A comparison of the amino acid sequences of the 2C proteins of poliovirus, foot-and-mouth disease virus, rhinovirus types 2 and 14, and encephalomyocarditis virus revealed a strong homology over regions totaling 115 residues. All of the mutations observed in guanidine-selected mutants were contained within this region. The amino acid region containing the mutations observed in poliovirus mutants resistant to 2.0 mM guanidine was compared with the homologous region in the other picornaviruses; a strong correlation was found between the amino acid present at this position and the sensitivity of the virus to 2.0 mM guanidine.

MeSH Terms
Amino Acid Sequence Base Sequence Chromosome Mapping Dose-Response Relationship, Drug Drug Resistance, Microbial Encephalomyocarditis virus/genetics Guanidine Guanidines/pharmacology Poliovirus/drug effects,genetics RNA, Viral/genetics Selection, Genetic Sequence Homology, Nucleic Acid Viral Proteins/genetics Virus Replication/drug effects
Chemicals
Guanidines RNA, Viral Viral Proteins Guanidine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Pincus S E
Diamond D C
Emini E A
Wimmer E
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49 references, click to expand
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
Published
1986-02-00
Pages
638-46
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC252779
Subset
IM
Grants
NIAID NIH HHS · AI-06920 · United States
NIAID NIH HHS · AI-15122 · United States
NCI NIH HHS · CA-28146 · United States
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