{"doi":"10.1371/journal.pcbi.0030029","title":"Synonymous Substitution Rates Predict HIV Disease Progression as a Result of Underlying Replication Dynamics","abstract":null,"journal":"PLoS Computational Biology","year":2007,"id":634889,"datarank":0.7525919755222388,"base_score":5.017279836814924,"endowment":5.017279836814924,"self_citation_contribution":0.7525919755222388,"citation_network_contribution":0.0,"self_endowment_contribution":0.7525919755222388,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":150,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1646878,"name":"Sergei L Kosakovsky Pond","orcid":null,"position":1,"is_corresponding":false},{"id":1646880,"name":"Alexei J Drummond","orcid":null,"position":2,"is_corresponding":false},{"id":1646882,"name":"Oliver G Pybus","orcid":null,"position":3,"is_corresponding":false},{"id":226135,"name":"Beth Shapiro","orcid":"0000-0002-2733-7776","position":4,"is_corresponding":false},{"id":1186462,"name":"Helena Barroso","orcid":"0000-0003-4098-5433","position":5,"is_corresponding":false},{"id":48733,"name":"Nuno Taveira","orcid":"0000-0003-0176-5585","position":6,"is_corresponding":false},{"id":34991,"name":"Andrew Rambaut","orcid":"0000-0003-4337-3707","position":7,"is_corresponding":false},{"id":36828,"name":"Philippe Lemey","orcid":"0000-0003-2826-5353","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Synonymous Substitution Rates Predict HIV Disease Progression as a Result of Underlying Replication Dynamics","abstract":"Upon HIV transmission, some patients develop AIDS in only a few months, while others remain disease free for 20 or more years. This variation in the rate of disease progression is poorly understood and has been attributed to host genetics, host immune responses, co-infection, viral genetics, and adaptation. Here, we develop a new \"relaxed-clock\" phylogenetic method to estimate absolute rates of synonymous and nonsynonymous substitution through time. We identify an unexpected association between the synonymous substitution rate of HIV and disease progression parameters. Since immune activation is the major determinant of HIV disease progression, we propose that this process can also determine viral generation times, by creating favourable conditions for HIV replication. These conclusions may apply more generally to HIV evolution, since we also observed an overall low synonymous substitution rate for HIV-2, which is known to be less pathogenic than HIV-1 and capable of tempering the detrimental effects of immune activation. Humoral immune responses, on the other hand, are the major determinant of nonsynonymous rate changes through time in the envelope gene, and our relaxed-clock estimates support a decrease in selective pressure as a consequence of immune system collapse.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17305421","pmcid":"PMC1797821","openalex_id":null,"authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"R56 AI047745","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI43638","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI047745","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI057167","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI47745","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI57167","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI36214","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"U01 AI043638","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"P30 AI036214","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R21 AI047745","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01AI057167-03","title":"Modeling HIV Escape from Neutralizing Antibody Respones"},{"funder_name":"Wellcome Trust","grant_id":"unidentified","title":"unidentified"},{"funder_name":"National Institutes of Health","grant_id":"5U01AI043638-09","title":"Southern California Primary Infection Program"},{"funder_name":"National Institutes of Health","grant_id":"5R01AI047745-08","title":"BIOMATHEMATICAL ANALYSIS OF VIRAL DYNAMICS AND EVOLUTION"},{"funder_name":"Fundação para a Ciência e a Tecnologia, I.P.","grant_id":"POCTI/ESP/48045/2002","title":"Neutralization profiles of sera from HIV-2-infected individuals: relationship to viral load and to the genetic and phenotypic diversity of virus quasispecies"},{"funder_name":"Wellcome Trust","grant_id":"","title":null}],"total_grants":16,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.0030029&type=printable","host_type":"publisher"},{"url":"https://dx.plos.org/10.1371/journal.pcbi.0030029","host_type":"publisher"},{"url":"https://lirias.kuleuven.be/handle/123456789/242644","host_type":"repository"},{"url":"https://figshare.com/articles/dataset/Synonymous_Substitution_Rates_Predict_HIV_Disease_Progression_as_a_Result_of_Underlying_Replication_Dynamics/152307","host_type":"repository"},{"url":"https://www.pure.ed.ac.uk/ws/files/7615835/PLOS_2007_Rambaut.pdf","host_type":"repository"},{"url":"https://doaj.org/article/fed2db51a5314baa8adf34588a897fb5","host_type":"repository"},{"url":"http://europepmc.org/articles/PMC1797821","host_type":"repository"},{"url":"https://ora.ox.ac.uk/objects/uuid:0f04da8a-34e9-4404-9084-5b1aa9d79eed","host_type":"repository"},{"url":"http://doi.org/10.1371/journal.pcbi.0030029","host_type":"repository"},{"url":"https://hdl.handle.net/20.500.11820/efe39b24-d34f-4ee9-a781-4b8e190286d8","host_type":"repository"},{"url":"http://hdl.handle.net/20.500.12613/5626","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC1797821","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC1797821?pdf=render","host_type":"Europe_PMC"},{"url":"https://doi.org/10.1371/journal.pcbi.0030029","host_type":""},{"url":"https://doi.org/10.1371/journal.pcbi.0030029.eor","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/17305421","host_type":""},{"url":"http://dx.doi.org/10.1371/journal.pcbi.0030029","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pcbi.0030029","host_type":""},{"url":"https://doi.org/doi:10.1371/journal.pcbi.0030029","host_type":""},{"url":"https://ora.ox.ac.uk/objects/uuid:2699111c-5904-41ec-aacf-a5994e6e9cfd","host_type":""},{"url":"https://ora.ox.ac.uk/objects/uuid:2760f305-0bf7-4f7b-a563-324549c1f615","host_type":""},{"url":"https://hdl.handle.net/10451/21396","host_type":""},{"url":"https://hdl.handle.net/10451/21395","host_type":""},{"url":"https://www.research.ed.ac.uk/en/publications/efe39b24-d34f-4ee9-a781-4b8e190286d8","host_type":""}],"fields_of_study":["0301 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activation","Biochemical Research Methods","NEUTRALIZING ANTIBODIES","Evolution, Molecular","Humans","Computer Simulation","Genetic Predisposition to Disease","Amino Acid Sequence","Codon","amino-acid sites","01 Mathematical Sciences","Science & Technology","Models, Genetic","molecular evolution","GENETIC DRIFT","Genetic Variation","06 Biological Sciences","Amino Acid Substitution","Virus Activation","Mathematical & Computational Biology","08 Information and Computing Sciences"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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