HIV-1 Replication Fitness of HLA-B*57/58:01 CTL Escape Variants Is Restored by the Accumulation of Compensatory Mutations in Gag
Publication Date
December 05, 2013
Journal
PLOS ONE
Authors
Esther F. Gijsbers, K. Anton Feenstra, Ad C. Van Nuenen, Marjon Navis, et al
Volume
8
Issue
12
Pages
e81235
DOI
https://dx.plos.org/10.1371/journal.pone.0081235
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0081235
Mendeley
http://www.mendeley.com/research/hiv1-replication-fitness-hlab575801-ctl-escape-variants-restored-accumulation-compensatory-mutations
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Mendeley | Further Information

{"title"=>"HIV-1 replication fitness of HLA-B*57/58:01 CTL Escape variants is restored by the accumulation of compensatory mutations in Gag", "type"=>"journal", "authors"=>[{"first_name"=>"Esther F.", "last_name"=>"Gijsbers", "scopus_author_id"=>"54794986500"}, {"first_name"=>"K.", "last_name"=>"Anton Feenstra", "scopus_author_id"=>"23099083800"}, {"first_name"=>"Ad C.", "last_name"=>"Van Nuenen", "scopus_author_id"=>"6506182226"}, {"first_name"=>"Marjon", "last_name"=>"Navis", "scopus_author_id"=>"6506344498"}, {"first_name"=>"Jaap", "last_name"=>"Heringa", "scopus_author_id"=>"55864715000"}, {"first_name"=>"Hanneke", "last_name"=>"Schuitemaker", "scopus_author_id"=>"7006687551"}, {"first_name"=>"Neeltje A.", "last_name"=>"Kootstra", "scopus_author_id"=>"6603966335"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"24339913", "doi"=>"10.1371/journal.pone.0081235", "sgr"=>"84891921477", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84891921477", "issn"=>"19326203", "pui"=>"372094769"}, "id"=>"91781df4-fd25-33cc-bb4a-c92717f413d8", "abstract"=>"Expression of HLA-B*57 and the closely related HLA-B*58:01 are associated with prolonged survival after HIV-1 infection. However, large differences in disease course are observed among HLA-B*57/58:01 patients. Escape mutations in CTL epitopes restricted by these HLA alleles come at a fitness cost and particularly the T242N mutation in the TW10 CTL epitope in Gag has been demonstrated to decrease the viral replication capacity. Additional mutations within or flanking this CTL epitope can partially restore replication fitness of CTL escape variants. Five HLA-B*57/58:01 progressors and 5 HLA-B*57/58:01 long-term nonprogressors (LTNPs) were followed longitudinally and we studied which compensatory mutations were involved in the restoration of the viral fitness of variants that escaped from HLA-B*57/58:01-restricted CTL pressure. The Sequence Harmony algorithm was used to detect homology in amino acid composition by comparing longitudinal Gag sequences obtained from HIV-1 patients positive and negative for HLA-B*57/58:01 and from HLA-B*57/58:01 progressors and LTNPs. Although virus isolates from HLA-B*57/58:01 individuals contained multiple CTL escape mutations, these escape mutations were not associated with disease progression. In sequences from HLA-B*57/58:01 progressors, 5 additional mutations in Gag were observed: S126N, L215T, H219Q, M228I and N252H. The combination of these mutations restored the replication fitness of CTL escape HIV-1 variants. Furthermore, we observed a positive correlation between the number of escape and compensatory mutations in Gag and the replication fitness of biological HIV-1 variants isolated from HLA-B*57/58:01 patients, suggesting that the replication fitness of HLA-B*57/58:01 escape variants is restored by accumulation of compensatory mutations.", "link"=>"http://www.mendeley.com/research/hiv1-replication-fitness-hlab575801-ctl-escape-variants-restored-accumulation-compensatory-mutations", "reader_count"=>25, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>3, "Researcher"=>3, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>3, "Researcher"=>3, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Other"=>1, "Student > Master"=>2, "Student > Bachelor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>14, "Medicine and Dentistry"=>2, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>14}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Hungary"=>1, "Japan"=>1}, "group_count"=>2}

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