{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:16:39Z","timestamp":1760188599357,"version":"build-2065373602"},"reference-count":46,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,5,25]],"date-time":"2019-05-25T00:00:00Z","timestamp":1558742400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/v11050479","type":"journal-article","created":{"date-parts":[[2019,5,26]],"date-time":"2019-05-26T23:07:27Z","timestamp":1558912047000},"page":"479","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of Mutational Tolerance of a Viral RNA\u2013Protein Interaction"],"prefix":"10.3390","volume":"11","author":[{"given":"Maria A.","family":"Prostova","sequence":"first","affiliation":[{"name":"Institute of Poliomyelitis, M. P. Chumakov Center for Research and Development of Immunobiological Products, Russian Academy of Sciences, 108819 Moscow, Russia"},{"name":"Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Smertina","sequence":"additional","affiliation":[{"name":"Institute of Poliomyelitis, M. P. Chumakov Center for Research and Development of Immunobiological Products, Russian Academy of Sciences, 108819 Moscow, Russia"},{"name":"Faculty of Fundamental Medicine, M. V. Lomonosov Moscow State University, 117192 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis V.","family":"Bakhmutov","sequence":"additional","affiliation":[{"name":"Institute of Poliomyelitis, M. P. Chumakov Center for Research and Development of Immunobiological Products, Russian Academy of Sciences, 108819 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna A.","family":"Gasparyan","sequence":"additional","affiliation":[{"name":"Institute of Poliomyelitis, M. P. Chumakov Center for Research and Development of Immunobiological Products, Russian Academy of Sciences, 108819 Moscow, Russia"},{"name":"Faculty of Biology, M. V. Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena V.","family":"Khitrina","sequence":"additional","affiliation":[{"name":"Institute of Poliomyelitis, M. P. Chumakov Center for Research and Development of Immunobiological Products, Russian Academy of Sciences, 108819 Moscow, Russia"},{"name":"A. N. Belozersky Institute of Physical-Chemical Biology, M. V. Lomonosov Moscow State University, 119899 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina S.","family":"Kolesnikova","sequence":"additional","affiliation":[{"name":"Institute of Poliomyelitis, M. P. Chumakov Center for Research and Development of Immunobiological Products, Russian Academy of Sciences, 108819 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna A.","family":"Shishova","sequence":"additional","affiliation":[{"name":"Institute of Poliomyelitis, M. P. Chumakov Center for Research and Development of Immunobiological Products, Russian Academy of Sciences, 108819 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anatoly P.","family":"Gmyl","sequence":"additional","affiliation":[{"name":"Institute of Poliomyelitis, M. P. Chumakov Center for Research and Development of Immunobiological Products, Russian Academy of Sciences, 108819 Moscow, Russia"},{"name":"Faculty of Biology, M. V. Lomonosov Moscow State University, 119991 Moscow, Russia"},{"name":"Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9743-8145","authenticated-orcid":false,"given":"Vadim I.","family":"Agol","sequence":"additional","affiliation":[{"name":"Institute of Poliomyelitis, M. P. Chumakov Center for Research and Development of Immunobiological Products, Russian Academy of Sciences, 108819 Moscow, Russia"},{"name":"A. N. Belozersky Institute of Physical-Chemical Biology, M. V. Lomonosov Moscow State University, 119899 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1146\/annurev.micro.51.1.151","article-title":"RNA virus mutations and fitness for survival","volume":"51","author":"Domingo","year":"1997","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13910","DOI":"10.1073\/pnas.96.24.13910","article-title":"Mutation rates among RNA viruses","volume":"96","author":"Drake","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9733","DOI":"10.1128\/JVI.00694-10","article-title":"Viral mutation rates","volume":"84","author":"Nebot","year":"2010","journal-title":"J. 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