Next Article in Journal
Inactivation of Dairy Bacteriophages by Thermal and Chemical Treatments
Previous Article in Journal
Animals as Reservoir for Human Norovirus
Open AccessArticle

Characterization of Mutational Tolerance of a Viral RNA–Protein Interaction

1
Institute of Poliomyelitis, M. P. Chumakov Center for Research and Development of Immunobiological Products, Russian Academy of Sciences, 108819 Moscow, Russia
2
Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia
3
Faculty of Fundamental Medicine, M. V. Lomonosov Moscow State University, 117192 Moscow, Russia
4
Faculty of Biology, M. V. Lomonosov Moscow State University, 119991 Moscow, Russia
5
A. N. Belozersky Institute of Physical-Chemical Biology, M. V. Lomonosov Moscow State University, 119899 Moscow, Russia
6
Sechenov First Moscow State Medical University, 119991 Moscow, Russia
*
Author to whom correspondence should be addressed.
Deceased.
Viruses 2019, 11(5), 479; https://doi.org/10.3390/v11050479
Received: 26 March 2019 / Revised: 20 May 2019 / Accepted: 22 May 2019 / Published: 25 May 2019
(This article belongs to the Section Animal Viruses)
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 reversions or compensatory mutations. Together with our study on the tolerance of oriL (Prostova et al., 2015), the results demonstrate that at least 42 out of 51 possible nucleotide replacements within the two relevant genomic regions are viability-compatible. These results provide new insights into structural aspects of an important viral function as well as into the general problems of viral mutational robustness and evolution. View Full-Text
Keywords: poliovirus; RNA; cis-elements; RNA/protein interaction; protease 3C; nucleotide/amino acid sequences; randomization; SELEX; mutational robustness; viability poliovirus; RNA; cis-elements; RNA/protein interaction; protease 3C; nucleotide/amino acid sequences; randomization; SELEX; mutational robustness; viability
Show Figures

Figure 1

MDPI and ACS Style

Prostova, M.A.; Smertina, E.; Bakhmutov, D.V.; Gasparyan, A.A.; Khitrina, E.V.; Kolesnikova, M.S.; Shishova, A.A.; Gmyl, A.P.; Agol, V.I. Characterization of Mutational Tolerance of a Viral RNA–Protein Interaction. Viruses 2019, 11, 479.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop