Mendeley | Further Information

{"title"=>"Experimental Estimation of the Effects of All Amino-Acid Mutations to HIV’s Envelope Protein on Viral Replication in Cell Culture", "type"=>"journal", "authors"=>[{"first_name"=>"Hugh K.", "last_name"=>"Haddox", "scopus_author_id"=>"57192805258"}, {"first_name"=>"Adam S.", "last_name"=>"Dingens", "scopus_author_id"=>"56768059900"}, {"first_name"=>"Jesse D.", "last_name"=>"Bloom", "scopus_author_id"=>"7201379306"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"pmid"=>"27959955", "doi"=>"10.1371/journal.ppat.1006114", "sgr"=>"85008164772", "scopus"=>"2-s2.0-85008164772", "issn"=>"15537374", "pui"=>"613938054"}, "id"=>"0d62ac98-6f7b-381e-88f2-b7c633100471", "abstract"=>"HIV is notorious for its capacity to evade immunity and anti-viral drugs through rapid sequence evolution. Knowledge of the functional effects of mutations to HIV is critical for understanding this evolution. HIV’s most rapidly evolving protein is its envelope (Env). Here we use deep mutational scanning to experimentally estimate the effects of all amino-acid mutations to Env on viral replication in cell culture. Most mutations are under purifying selec- tion in our experiments, although a few sites experience strong selection for mutations that enhance HIV’s replication in cell culture.Wecompare our experimental measurements of each site’s preference for each amino acid to the actual frequencies of these amino acids in naturally occurring HIV sequences. Our measured amino-acid preferences correlate with amino-acid frequencies in natural sequences for most sites. However, our measured prefer- ences are less concordant with natural amino-acid frequencies at surface-exposed sites that are subject to pressures absent from our experiments such as antibody selection. Our data enable us to quantify the inherent mutational tolerance of each site in Env.Weshow that the epitopes of broadly neutralizing antibodies have a significantly reduced inherent capacity to tolerate mutations, rigorously validating a pervasive idea in the field. Overall, our results help disentangle the role of inherent functional constraints and external selection pressures in shaping Env’s evolution. Author", "link"=>"http://www.mendeley.com/research/experimental-estimation-effects-aminoacid-mutations-hivs-envelope-protein-viral-replication-cell-cul", "reader_count"=>45, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Librarian"=>1, "Researcher"=>17, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>3, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Librarian"=>1, "Researcher"=>17, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>12, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>3, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>16, "Agricultural and Biological Sciences"=>19, "Arts and Humanities"=>1, "Physics and Astronomy"=>1, "Chemistry"=>1, "Social Sciences"=>1, "Computer Science"=>2, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>19}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>16}, "Unspecified"=>{"Unspecified"=>3}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"United States"=>1, "France"=>1}, "group_count"=>1}

CrossRef

• http://doi.org/10.1093/ve/vex003
• http://doi.org/10.1016/j.cell.2019.06.030
• http://doi.org/10.4049/jimmunol.1800343
• http://doi.org/10.7717/peerj.3657
• http://doi.org/10.1073/pnas.1806133115
• http://doi.org/10.1371/journal.pgen.1007420
• http://doi.org/10.7554/eLife.34420
• http://doi.org/10.1016/j.chom.2017.05.003
• http://doi.org/10.1128/JVI.00219-19
• http://doi.org/10.1016/j.immuni.2018.12.017
• http://doi.org/10.1073/pnas.1717765115
• http://doi.org/10.1093/molbev/msx251
• http://doi.org/10.1084/jem.20180936
• http://doi.org/10.1038/s41576-018-0069-z
• http://doi.org/10.1128/mBio.01050-17
• http://doi.org/10.3390/v11050439
• http://doi.org/10.1016/j.coviro.2018.12.006
• http://doi.org/10.1371/journal.ppat.1006271
• http://doi.org/10.1128/JVI.00698-17
• http://doi.org/10.1371/journal.ppat.1007159
• http://doi.org/10.1093/molbev/msx095
• http://doi.org/10.1093/molbev/msy088
• http://doi.org/10.1093/ve/vey029

Scopus | Further Information

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