Characterization of mutational tolerance of a viral RNA–protein interaction
Prostova M. A., Smertina E., Bakhmutov D. V., Gasparyan A. A., Khitrina E. V., Kolesnikova M. S., Shishova A. A., Gmy'l` A. P., Agol V. I.
Viruses
Vol.11, Issue5, Num.479
Опубликовано: 2019
Тип ресурса: Статья
Аннотация:
Replication of RNA viruses is generally markedly error-prone. Nevertheless, these viruses usually retain their identity under more or less constant conditions due to different mechanisms of mutation tolerance. However, there exists only limited information on quantitative aspects of the mutational tolerance of distinct viral functions. To address this problem, we used here as a model the interaction between a replicative cis-acting RNA element (oriL) of poliovirus and its ligand (viral protein 3CD). The mutational tolerance of a conserved tripeptide of 3CD, directly involved in this interaction, was investigated. Randomization of the relevant codons and reverse genetics were used to define the space of viability-compatible sequences. Surprisingly, at least 11 different amino acid substitutions in this tripeptide were not lethal. Several altered viruses exhibited wild-type-like phenotypes, whereas debilitated (but viable) genomes could increase their fitness by the acquisition of revers
Ключевые слова:
Cis-elements; Mutational robustness; Nucleotide/amino acid sequences; Poliovirus; Protease 3C; Randomization; RNA; RNA/protein interaction; SELEX; Viability
tripeptide; unclassified drug; viral protein; viral protein 3CD; virus RNA; RNA binding protein; virus RNA; amino acid sequence; amino acid substitution; Article; codon; controlled study; gene sequence; nonhuman; nucleotide sequence; open reading frame; phenotype; Poliomyelitis virus; protein purification; protein RNA binding; protein structure; reverse genetics; revertant; virus genome; chemistry; genetics; host pathogen interaction; human; metabolism; mutation; physiology; plasmid; RNA virus; RNA virus infection; virology; virus replication; Base Sequence; Genome, Viral; Host-Pathogen Interactions; Humans; Mutation; Plasmids; RNA Virus Infections; RNA Viruses; RNA, Viral; RNA-Binding Proteins; Virus Replication
Язык текста: Английский
ISSN: 1999-4915
Prostova M. A.
Smertina E.
Bakhmutov D. V.
Gasparyan A. A.
Khitrina E. V.
Kolesnikova M. S.
Shishova A. A.
Gmy'l` A. P. Anatolij Petrovich 1966-
Agol V. I.
Простова М. А.
Смертина Е.
Бахмутов Д. В.
Гаспарян А. А.
Хитрина Е. В.
Колесникова М. С.
Шишова А. А.
Гмыль А. П. Анатолий Петрович 1966-
Агол В. И.
Characterization of mutational tolerance of a viral RNA–protein interaction
Текст визуальный непосредственный
Viruses
Vol.11, Issue5 Num.479
2019
Статья
Cis-elements Mutational robustness Nucleotide/amino acid sequences Poliovirus Protease 3C Randomization RNA RNA/protein interaction SELEX Viability
tripeptide unclassified drug viral protein viral protein 3CD virus RNA RNA binding protein virus RNA amino acid sequence amino acid substitution Article codon controlled study gene sequence nonhuman nucleotide sequence open reading frame phenotype Poliomyelitis virus protein purification protein RNA binding protein structure reverse genetics revertant virus genome chemistry genetics host pathogen interaction human metabolism mutation physiology plasmid RNA virus RNA virus infection virology virus replication Base Sequence Genome, Viral Host-Pathogen Interactions Humans Mutation Plasmids RNA Virus Infections RNA Viruses RNA, Viral RNA-Binding Proteins Virus Replication
Replication of RNA viruses is generally markedly error-prone. Nevertheless, these viruses usually retain their identity under more or less constant conditions due to different mechanisms of mutation tolerance. However, there exists only limited information on quantitative aspects of the mutational tolerance of distinct viral functions. To address this problem, we used here as a model the interaction between a replicative cis-acting RNA element (oriL) of poliovirus and its ligand (viral protein 3CD). The mutational tolerance of a conserved tripeptide of 3CD, directly involved in this interaction, was investigated. Randomization of the relevant codons and reverse genetics were used to define the space of viability-compatible sequences. Surprisingly, at least 11 different amino acid substitutions in this tripeptide were not lethal. Several altered viruses exhibited wild-type-like phenotypes, whereas debilitated (but viable) genomes could increase their fitness by the acquisition of revers