Estimating the Fitness Cost of Escape from HLA Presentation in HIV-1 Protease and Reverse Transcriptase
- Publication Date
- May 24, 2012
- Journal
- PLOS Computational Biology
- Authors
- Rafal Mostowy, Roger D. Kouyos, Ilka Hoof, Trevor Hinkley, et al
- Volume
- 8
- Issue
- 5
- Pages
- e1002525
- DOI
- https://dx.plos.org/10.1371/journal.pcbi.1002525
- Publisher URL
- http://journals.plos.org/ploscompbiol/article?id=10.1371%2Fjournal.pcbi.1002525
- PubMed
- http://www.ncbi.nlm.nih.gov/pubmed/22654656
- PubMed Central
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359966
- Europe PMC
- http://europepmc.org/abstract/MED/22654656
- Web of Science
- 000305964600032
- Scopus
- 84863680755
- Mendeley
- http://www.mendeley.com/research/estimating-fitness-cost-escape-hla-presentation-hiv1-protease-reverse-transcriptase
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Mendeley | Further Information
{"title"=>"Estimating the fitness cost of escape from hla presentation in HIV-1 protease and reverse transcriptase", "type"=>"journal", "authors"=>[{"first_name"=>"Rafal", "last_name"=>"Mostowy", "scopus_author_id"=>"36139106800"}, {"first_name"=>"Roger D.", "last_name"=>"Kouyos", "scopus_author_id"=>"14023112100"}, {"first_name"=>"Ilka", "last_name"=>"Hoof", "scopus_author_id"=>"24597293400"}, {"first_name"=>"Trevor", "last_name"=>"Hinkley", "scopus_author_id"=>"23050628100"}, {"first_name"=>"Mojgan", "last_name"=>"Haddad", "scopus_author_id"=>"35955943600"}, {"first_name"=>"Jeannette M.", "last_name"=>"Whitcomb", "scopus_author_id"=>"7005226522"}, {"first_name"=>"Christos J.", "last_name"=>"Petropoulos", "scopus_author_id"=>"35464017000"}, {"first_name"=>"Can", "last_name"=>"Keşmir", "scopus_author_id"=>"6701789184"}, {"first_name"=>"Sebastian", "last_name"=>"Bonhoeffer", "scopus_author_id"=>"7005099220"}], "year"=>2012, "source"=>"PLoS Computational Biology", "identifiers"=>{"scopus"=>"2-s2.0-84863680755", "pui"=>"365220683", "pmid"=>"22654656", "issn"=>"1553734X", "isbn"=>"1553-7358 (Electronic)\r1553-734X (Linking)", "doi"=>"10.1371/journal.pcbi.1002525", "sgr"=>"84863680755"}, "id"=>"7ff61933-9d92-3903-94af-a072ebdc0a38", "abstract"=>"Human immunodeficiency virus (HIV-1) is, like most pathogens, under selective pressure to escape the immune system of its host. In particular, HIV-1 can avoid recognition by cytotoxic T lymphocytes (CTLs) by altering the binding affinity of viral peptides to human leukocyte antigen (HLA) molecules, the role of which is to present those peptides to the immune system. It is generally assumed that HLA escape mutations carry a replicative fitness cost, but these costs have not been quantified. In this study, we assess the replicative cost of mutations which are likely to escape presentation by HLA molecules in the region of HIV-1 protease and reverse transcriptase. Specifically, we combine computational approaches for prediction of in vitro replicative fitness and peptide binding affinity to HLA molecules. We find that mutations which impair binding to HLA-A molecules tend to have lower in vitro replicative fitness than mutations which do not impair binding to HLA-A molecules, suggesting that HLA-A escape mutations carry higher fitness costs than non-escape mutations. We argue that the association between fitness and HLA-A binding impairment is probably due to an intrinsic cost of escape from HLA-A molecules, and these costs are particularly strong for HLA-A alleles associated with efficient virus control. Counter-intuitively, we do not observe a significant effect in the case of HLA-B, but, as discussed, this does not argue against the relevance of HLA-B in virus control. Overall, this article points to the intriguing possibility that HLA-A molecules preferentially target more conserved regions of HIV-1, emphasizing the importance of HLA-A genes in the evolution of HIV-1 and RNA viruses in general.", "link"=>"http://www.mendeley.com/research/estimating-fitness-cost-escape-hla-presentation-hiv1-protease-reverse-transcriptase", "reader_count"=>22, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Student > Master"=>4}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>6, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Student > Master"=>4}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>2, "Physics and Astronomy"=>1, "Social Sciences"=>1, "Computer Science"=>2, "Immunology and Microbiology"=>3, "Linguistics"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Computer Science"=>{"Computer Science"=>2}, "Linguistics"=>{"Linguistics"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}}, "reader_count_by_country"=>{"United States"=>1, "India"=>1}, "group_count"=>1}CrossRef
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Scopus | Further Information
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Relative Metric
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