The Mutational Robustness of Influenza A Virus
Publication Date
August 29, 2016
Journal
PLOS Pathogens
Authors
Elisa Visher, Shawn E. Whitefield, John T. Mc Crone, William Fitzsimmons, et al
Volume
12
Issue
8
Pages
e1005856
DOI
https://dx.plos.org/10.1371/journal.ppat.1005856
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1005856
Scopus
84984860940
Mendeley
http://www.mendeley.com/research/mutational-robustness-influenza-virus
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Mendeley | Further Information

{"title"=>"The Mutational Robustness of Influenza A Virus", "type"=>"journal", "authors"=>[{"first_name"=>"Elisa", "last_name"=>"Visher", "scopus_author_id"=>"57190965265"}, {"first_name"=>"Shawn E.", "last_name"=>"Whitefield", "scopus_author_id"=>"57190967204"}, {"first_name"=>"John T.", "last_name"=>"McCrone", "scopus_author_id"=>"57189030254"}, {"first_name"=>"William", "last_name"=>"Fitzsimmons", "scopus_author_id"=>"57190968393"}, {"first_name"=>"Adam S.", "last_name"=>"Lauring", "scopus_author_id"=>"6603652630"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537374", "isbn"=>"1553-7366", "pmid"=>"27571422", "scopus"=>"2-s2.0-84984860940", "pui"=>"611987857", "doi"=>"10.1371/journal.ppat.1005856", "sgr"=>"84984860940"}, "id"=>"c4219a08-fd24-341d-86bb-144a99272b9d", "abstract"=>"A virus' mutational robustness is described in terms of the strength and distribution of the mutational fitness effects, or MFE. The distribution of MFE is central to many questions in evolutionary theory and is a key parameter in models of molecular evolution. Here we define the mutational fitness effects in influenza A virus by generating 128 viruses, each with a single nucleotide mutation. In contrast to mutational scanning approaches, this strategy allowed us to unambiguously assign fitness values to individual mutations. The presence of each desired mutation and the absence of additional mutations were verified by next generation sequencing of each stock. A mutation was considered lethal only after we failed to rescue virus in three independent transfections. We measured the fitness of each viable mutant relative to the wild type by quantitative RT-PCR following direct competition on A549 cells. We found that 31.6% of the mutations in the genome-wide dataset were lethal and that the lethal fraction did not differ appreciably between the HA- and NA-encoding segments and the rest of the genome. Of the viable mutants, the fitness mean and standard deviation were 0.80 and 0.22 in the genome-wide dataset and best modeled as a beta distribution. The fitness impact of mutation was marginally lower in the segments coding for HA and NA (0.88 ± 0.16) than in the other 6 segments (0.78 ± 0.24), and their respective beta distributions had slightly different shape parameters. The results for influenza A virus are remarkably similar to our own analysis of CirSeq-derived fitness values from poliovirus and previously published data from other small, single stranded DNA and RNA viruses. These data suggest that genome size, and not nucleic acid type or mode of replication, is the main determinant of viral mutational fitness effects.", "link"=>"http://www.mendeley.com/research/mutational-robustness-influenza-virus", "reader_count"=>38, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>4, "Researcher"=>11, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>4, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>4, "Researcher"=>11, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>4, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>1, "Environmental Science"=>2, "Biochemistry, Genetics and Molecular Biology"=>8, "Agricultural and Biological Sciences"=>16, "Medicine and Dentistry"=>2, "Veterinary Science and Veterinary Medicine"=>1, "Chemistry"=>1, "Social Sciences"=>1, "Immunology and Microbiology"=>5}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Unspecified"=>{"Unspecified"=>1}, "Environmental Science"=>{"Environmental Science"=>2}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>0}

Scopus | Further Information

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