The Role of Recombination for the Coevolutionary Dynamics of HIV and the Immune Response
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{"title"=>"The role of recombination for the coevolutionary dynamics of HIV and the immune response", "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"=>"David", "last_name"=>"Fouchet", "scopus_author_id"=>"55648990000"}, {"first_name"=>"Sebastian", "last_name"=>"Bonhoeffer", "scopus_author_id"=>"7005099220"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pmid"=>"21364750", "pui"=>"361327598", "scopus"=>"2-s2.0-79951974746", "doi"=>"10.1371/journal.pone.0016052", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"79951974746"}, "id"=>"6ceb804e-19f0-34b6-a9b6-0560e3be2c20", "abstract"=>"The evolutionary implications of recombination in HIV remain not fully understood. A plausible effect could be an enhancement of immune escape from cytotoxic T lymphocytes (CTLs). In order to test this hypothesis, we constructed a population dynamic model of immune escape in HIV and examined the viral-immune dynamics with and without recombination. Our model shows that recombination (i) increases the genetic diversity of the viral population, (ii) accelerates the emergence of escape mutations with and without compensatory mutations, and (iii) accelerates the acquisition of immune escape mutations in the early stage of viral infection. We see a particularly strong impact of recombination in systems with broad, non-immunodominant CTL responses. Overall, our study argues for the importance of recombination in HIV in allowing the virus to adapt to changing selective pressures as imposed by the immune system and shows that the effect of recombination depends on the immunodominance pattern of effector T cell responses.", "link"=>"http://www.mendeley.com/research/role-recombination-coevolutionary-dynamics-hiv-immune-response", "reader_count"=>48, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>4, "Researcher"=>15, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>5, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>4, "Researcher"=>15, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>5, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Unspecified"=>3, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>4, "Mathematics"=>5, "Agricultural and Biological Sciences"=>25, "Medicine and Dentistry"=>4, "Physics and Astronomy"=>1, "Computer Science"=>1, "Linguistics"=>1, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Chemistry"=>{"Chemistry"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>25}, "Computer Science"=>{"Computer Science"=>1}, "Linguistics"=>{"Linguistics"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Mathematics"=>{"Mathematics"=>5}, "Unspecified"=>{"Unspecified"=>3}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"Netherlands"=>1, "Hungary"=>1, "United States"=>2, "Mexico"=>1, "South Africa"=>2, "France"=>1, "India"=>1, "Spain"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/796806"], "description"=>"<p>In both panels the time of emergence of mutants with a given number of escape mutations is shown. Orange and blue bars correspond to runs with and without recombination, respectively. A shows the time of appearance of E escapes (escapes at the escape locus). Panel B shows the time of appearance of EC escapes (escapes at the escape and compensatory locus). The simulations show that recombination accelerates the emergence of escape mutations. Parameters used: , ; the others are defined in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016052#pone-0016052-t001\" target=\"_blank\">Table 1</a>. The plot shows an average of 10000 simulation runs.</p>", "links"=>[], "tags"=>["times", "successive", "accumulations"], "article_id"=>467176, "categories"=>["Virology", "Biochemistry", "Infectious Diseases", "Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Rafal Mostowy", "Roger D. Kouyos", "David Fouchet", "Sebastian Bonhoeffer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0016052.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_average_times_of_appearance_of_successive_accumulations_of_escape_mutations_/467176", "title"=>"The average times of appearance of successive accumulations of escape mutations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 20:25:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/796977"], "description"=>"<p>Figures are plotted as a function of mean avidity and variance of avidity of the CTL response. Panel A shows the mean diversity of the CTL population which decreases with increasing mean (except for an initial increase in avidity) and decreasing variance in avidity. Panel B shows the mean number of escapes during infection without recombination after 1 yr. of infection, which has an optimum for a given mean avidity of response and correlates well with the diversity of the CTL response in panel A. Panel C shows the factor of increase in the number of escapes after one year (cf. panel B) due to recombination, which is the strongest for broad and even responses. Panels D and E show the time of appearance (days) of the full escape variant without and with recombination, respectively. The hatched areas show runs in which the full escape mutant did not appear within the time of 1000 days. The impact of recombination on the time of emergence of the full escape mutant, shown in panel F, corresponds well to the impact of recombination on the number of escape mutations after one year, shown in panel C. The mean and variance of log avidities ( and , respectively) plotted in all panels are defined in each simulation, and the distribution of avidity values is drawn from a uniform distribution in each simulation run between and . The parameters used: , , . All other parameters are given in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016052#pone-0016052-t001\" target=\"_blank\">Table 1</a>. Each point in the plot shows an average of 5000 simulation runs.</p>", "links"=>[], "tags"=>["genetics and genomics", "Virology", "Infectious diseases", "Computational biology", "Evolutionary biology", "Biochemistry"], "article_id"=>467344, "categories"=>["Virology", "Biochemistry", "Infectious Diseases", "Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Rafal Mostowy", "Roger D. Kouyos", "David Fouchet", "Sebastian Bonhoeffer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0016052.g005", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CTL_dynamics_and_the_impact_of_recombination_/467344", "title"=>"CTL dynamics and the impact of recombination.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 20:26:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/796894"], "description"=>"<p>Orange and blue bars correspond to runs with and without recombination, respectively. Panel A shows the viral diversity as a number of strains in the population (results for other measures of diversity were qualitatively similar). It can be seen that recombination has a significant impact on diversity regardless of the stage of infection. Panel B shows the mean number of escapes measured by the mean HD at the escape loci. The panel shows that recombination accelerates the evolution of immune escape in the virus in the early phase of infection because it accelerates the acquisition of the escape mutations when they are beneficial. Note that the strain with mutations at all loci (HD = 30) has arisen only in the runs with recombination (one blue bar missing in panel B). The parameters are identical as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016052#pone-0016052-g003\" target=\"_blank\">Fig. 3</a> and the plot also shows an average of 10000 simulation runs.</p>", "links"=>[], "tags"=>["recombination", "chosen", "parameters"], "article_id"=>467260, "categories"=>["Virology", "Biochemistry", "Infectious Diseases", "Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Rafal Mostowy", "Roger D. Kouyos", "David Fouchet", "Sebastian Bonhoeffer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0016052.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effect_of_recombination_on_chosen_parameters_of_the_model_/467260", "title"=>"The effect of recombination on chosen parameters of the model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 20:25:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/797073"], "description"=>"<p>Assumed parameter values for HIV dynamics.</p>", "links"=>[], "tags"=>["parameter", "hiv"], "article_id"=>467447, "categories"=>["Virology", "Biochemistry", "Infectious Diseases", "Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Rafal Mostowy", "Roger D. Kouyos", "David Fouchet", "Sebastian Bonhoeffer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0016052.t001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Assumed_parameter_values_for_HIV_dynamics_/467447", "title"=>"Assumed parameter values for HIV dynamics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 20:26:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/796717"], "description"=>"<p>Simulation runs without recombination are shown with solid lines, and with recombination with dashed lines. Plotted are frequencies of escapes at all loci as a function of time, and in each case three chosen loci are printed in colour. Panel A shows an example simulation run for a parameter setting in which the impact of recombination is strong. Panel B shows an example simulation run for a parameter setting in which the impact of recombination is weak. Recombination mostly, but not always, accelerates the emergence and fixation of immune escapes. Parameters used in panel A: , , . Parameters used in panel B: , ; the remaining parameters are the same and are defined in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0016052#pone-0016052-t001\" target=\"_blank\">Table 1</a>.</p>", "links"=>[], "tags"=>["simulation", "runs"], "article_id"=>467091, "categories"=>["Virology", "Biochemistry", "Infectious Diseases", "Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Rafal Mostowy", "Roger D. Kouyos", "David Fouchet", "Sebastian Bonhoeffer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0016052.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Example_simulation_runs_of_the_virus_escape_dynamics_/467091", "title"=>"Example simulation runs of the virus escape dynamics.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 20:24:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/796604"], "description"=>"<p>Panel A: Recombination in HIV occurs in virions that contain two non-identical copies of RNA. During reverse transcription, one or more crossover events between the two strands can take place and result in recombination. Panel B: Immune escape of the infecting virus is modelled by assuming that of the epitopes presented on the surface of infected cells are recognised by the CD8+ T cells. The figure shows a situation for and an infected cell , which contains two epitopes recognised by the immune system () and one epitope that escapes the surveillance of the effector T cells (). Panel C: Escape from immune recognition comes at a fitness cost for the virus, and thus we assume that an escape mutation impairs the reproductive capacity of the pathogen (blue bar). A compensatory mutation partially restores the fitness cost (green bar). In the absence of the escape mutation, the compensatory mutation not only decreases the replicative capacity of the virus but also does not confer immune-resistance (yellow bar).</p>", "links"=>[], "tags"=>["recombination"], "article_id"=>466975, "categories"=>["Virology", "Biochemistry", "Infectious Diseases", "Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Rafal Mostowy", "Roger D. Kouyos", "David Fouchet", "Sebastian Bonhoeffer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0016052.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_model_of_recombination_in_HIV_/466975", "title"=>"The model of recombination in HIV.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 20:23:57"}

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Relative Metric

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