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• {"link"=>{"url"=>"http://www.citeulike.org/user/memerman/article/12092433"}, "post_time"=>"2013-02-28 23:31:26", "tag"=>["dengue_virus", "evolution"], "linkout"=>{"type"=>"DOI", "url"=>"http://dx.doi.org/10.1371/journal.ppat.1003193"}, "username"=>"memerman", "article_id"=>"12092433"}

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{"title"=>"Phylodynamic Analysis of the Emergence and Epidemiological Impact of Transmissible Defective Dengue Viruses", "type"=>"journal", "authors"=>[{"first_name"=>"Ruian", "last_name"=>"Ke", "scopus_author_id"=>"55440985300"}, {"first_name"=>"John", "last_name"=>"Aaskov", "scopus_author_id"=>"7003983570"}, {"first_name"=>"Edward C.", "last_name"=>"Holmes", "scopus_author_id"=>"55535773400"}, {"first_name"=>"James O.", "last_name"=>"Lloyd-Smith", "scopus_author_id"=>"6602998795"}], "year"=>2013, "source"=>"PLoS Pathogens", "identifiers"=>{"sgr"=>"84879727124", "doi"=>"10.1371/journal.ppat.1003193", "issn"=>"15537366", "pui"=>"369459541", "isbn"=>"1553-7374 (Electronic) 1553-7366 (Linking)", "pmid"=>"23468631", "scopus"=>"2-s2.0-84879727124"}, "id"=>"47985880-553f-38a3-bad6-ed5d8da07051", "abstract"=>"Intra-host sequence data from RNA viruses have revealed the ubiquity of defective viruses in natural viral populations, sometimes at surprisingly high frequency. Although defective viruses have long been known to laboratory virologists, their relevance in clinical and epidemiological settings has not been established. The discovery of long-term transmission of a defective lineage of dengue virus type 1 (DENV-1) in Myanmar, first seen in 2001, raised important questions about the emergence of transmissible defective viruses and their role in viral epidemiology. By combining phylogenetic analyses and dynamical modeling, we investigate how evolutionary and ecological processes at the intra-host and inter-host scales shaped the emergence and spread of the defective DENV-1 lineage. We show that this lineage of defective viruses emerged between June 1998 and February 2001, and that the defective virus was transmitted primarily through co-transmission with the functional virus to uninfected individuals. We provide evidence that, surprisingly, this co-transmission route has a higher transmission potential than transmission of functional dengue viruses alone. Consequently, we predict that the defective lineage should increase overall incidence of dengue infection, which could account for the historically high dengue incidence reported in Myanmar in 2001-2002. Our results show the unappreciated potential for defective viruses to impact the epidemiology of human pathogens, possibly by modifying the virulence-transmissibility trade-off, or to emerge as circulating infections in their own right. They also demonstrate that interactions between viral variants, such as complementation, can open new pathways to viral emergence.", "link"=>"http://www.mendeley.com/research/phylodynamic-analysis-emergence-epidemiological-impact-transmissible-defective-dengue-viruses", "reader_count"=>93, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>28, "Student > Doctoral Student"=>8, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>4, "Student > Master"=>12, "Other"=>2, "Student > Bachelor"=>8, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>28, "Student > Doctoral Student"=>8, "Student > Ph. D. Student"=>25, "Student > Postgraduate"=>4, "Student > Master"=>12, "Other"=>2, "Student > Bachelor"=>8, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>7, "Agricultural and Biological Sciences"=>57, "Veterinary Science and Veterinary Medicine"=>1, "Chemical Engineering"=>1, "Computer Science"=>1, "Decision Sciences"=>1, "Engineering"=>3, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>6, "Mathematics"=>2, "Medicine and Dentistry"=>8, "Social Sciences"=>1, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Social Sciences"=>{"Social Sciences"=>1}, "Decision Sciences"=>{"Decision Sciences"=>1}, "Mathematics"=>{"Mathematics"=>2}, "Unspecified"=>{"Unspecified"=>7}, "Environmental Science"=>{"Environmental Science"=>1}, "Chemical Engineering"=>{"Chemical Engineering"=>1}, "Engineering"=>{"Engineering"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>57}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Colombia"=>1, "Belgium"=>1, "United States"=>5, "United Kingdom"=>4, "Malaysia"=>1, "Chile"=>1, "Spain"=>1}, "group_count"=>12}

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CrossRef

• http://doi.org/10.1016/j.meegid.2018.04.032
• http://doi.org/10.1128/JVI.02675-13
• http://doi.org/10.1371/journal.pcbi.1006668
• http://doi.org/10.1371/journal.pone.0189554
• http://doi.org/10.1128/JVI.03265-14
• http://doi.org/10.1128/JVI.00807-16
• http://doi.org/10.1111/eva.12554
• http://doi.org/10.1128/mBio.01239-16
• http://doi.org/10.3390/v12050558
• http://doi.org/10.1128/JVI.02921-15
• http://doi.org/10.1371/journal.ppat.1004874
• http://doi.org/10.1016/j.tim.2017.02.003
• http://doi.org/10.1146/annurev-virology-101416-041718
• http://doi.org/10.3389/fmicb.2018.02942
• http://doi.org/10.1016/j.virol.2014.08.013
• http://doi.org/10.3389/fmicb.2020.01371
• http://doi.org/10.1080/15459624.2019.1591626
• http://doi.org/10.1016/j.tim.2013.05.004
• http://doi.org/10.7554/eLife.13974
• http://doi.org/10.1111/jeb.13225
• http://doi.org/10.1016/j.virusres.2019.02.015
• http://doi.org/10.1073/pnas.1324194111
• http://doi.org/10.1128/JVI.03193-13
• http://doi.org/10.1261/rna.066910.118
• http://doi.org/10.1186/s13036-016-0033-4
• http://doi.org/10.1016/j.tibtech.2014.06.006
• http://doi.org/10.1016/j.meegid.2016.04.025

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PubMed Central

• 4020047
• 3958049
• 4019098
• 4403435
• 4810721
• 4439088
• 4805539

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• {"id"=>"307589239313403905", "text"=>"Phylodynamic Analysis of the Emergence and Epidemiological Impact of Transmissible Defective Dengue Viruses http://t.co/1H0G0sSpna", "created_at"=>"2013-03-01T20:32:44Z", "user"=>"TSmieszek", "user_name"=>"Timo Smieszek", "user_profile_image"=>"http://a0.twimg.com/profile_images/3288794386/c4aec9d48c2a3acd2dddf1f1fe57ba82_normal.jpeg"}
• {"id"=>"307692680962535426", "text"=>"Phylodynamic Analysis of the Emergence and Epidemiological Impact of Transmissible Defective Dengue Viruses http://t.co/LLWxbJzdVb #Dengue", "created_at"=>"2013-03-02T03:23:46Z", "user"=>"PLOSPathogens", "user_name"=>"PLOS Pathogens", "user_profile_image"=>"http://a0.twimg.com/profile_images/2912874074/63b57ae4553820ea836f001cca52eaf5_normal.jpeg"}
• {"id"=>"308032784323194881", "text"=>"\"Defective\" Virus Leads to Epidemic of Dengue Fever... http://t.co/GjY7FzjhUG http://t.co/lFGRsc6mzn", "created_at"=>"2013-03-03T01:55:13Z", "user"=>"eduardorodbio", "user_name"=>"Eduardo Rodríguez R.", "user_profile_image"=>"http://a0.twimg.com/profile_images/1482100912/P3240018__2__normal.jpg"}
• {"id"=>"309389381947502592", "text"=>"http://t.co/pg8YAAFWOE", "created_at"=>"2013-03-06T19:45:51Z", "user"=>"ststoddard", "user_name"=>"Steven T. Stoddard", "user_profile_image"=>"http://a0.twimg.com/profile_images/1571880673/IMG_0096_normal.JPG"}
• {"id"=>"309688799556931586", "text"=>"#PLOSPathogens: Phylodynamic Analysis of the Emergence & Epidemiological Impact of Transmissible Defective #Dengue... http://t.co/cJVJMyFuiB", "created_at"=>"2013-03-07T15:35:38Z", "user"=>"DengueInfo", "user_name"=>"DengueInfo", "user_profile_image"=>"http://a0.twimg.com/profile_images/1693190779/Avatar_Twitter_Sanofi_Pasteur_Dengue_Info_normal.jpg"}
• {"id"=>"310750963633905665", "text"=>"#PLOSPathogens: Phylodynamic Analysis of Emergence & Epidemiological Impact of Transmissible Defective Dengue Viruses http://t.co/4QsA4ri9pG", "created_at"=>"2013-03-10T13:56:17Z", "user"=>"bruexpat", "user_name"=>"Michael Greenberg", "user_profile_image"=>"http://a0.twimg.com/profile_images/426502315/avian_flu_virus_normal.jpg"}
• {"id"=>"381019797594865665", "text"=>"How do defective viruses persist? DEN-1 strain piggy-backed functional dengue strains #PLOSPathogens #cotransmission http://t.co/nlHcP87giI", "created_at"=>"2013-09-20T11:39:33Z", "user"=>"emble64", "user_name"=>"Emily C Griffiths", "user_profile_image"=>"http://a0.twimg.com/profile_images/2861725321/e60bae27fb1bb3d07080cd8e49fd6d37_normal.jpeg"}

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• {"files"=>["https://ndownloader.figshare.com/files/973718"], "description"=>"<p>(<b>A</b>) Table showing the number of sequences belonging to each lineage, from the multiple isolates derived from each individual. (<b>B</b>) The evolutionary and transmission dynamics of DENV-1 isolates revealed by the MCC tree. The scale bar shows the time in years when the samples were taken. The numbers at the root of the stop-codon clade of the tree show the estimated time in years (and 95% credible intervals) of the time to common ancestry of the stop-codon lineage and the wt-1 lineage. The stop-codon lineage sequences are color-coded in blue, and the wt-1 lineage sequences that were isolated from tDP infected individuals are in red. The green dashed box (in both panels) shows the sequences that are descendants of the functional DENV-1 genotype that generated the stop-codon lineage. The patient numbers of the consensus sequences derived from multiple intra-host viral isolates are followed by their lineage identification, i.e. ‘_1’,‘_2’ and ‘_stop’. The patient numbers of the 8 additional sequences are in gray italic font.</p>", "links"=>[], "tags"=>["transmitted", "defective", "particles", "individuals", "infected", "viruses", "genetically", "stop-codon"], "article_id"=>642003, "categories"=>["Virology", "Biological Sciences", "Microbiology", "Evolutionary Biology"], "users"=>["Ruian Ke", "John Aaskov", "Edward C. Holmes", "James O. Lloyd-Smith"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003193.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_transmitted_defective_particles_tDP_are_detected_in_individuals_infected_by_functional_viruses_that_are_genetically_close_related_to_the_stop_codon_lineage_/642003", "title"=>"The transmitted defective particles (tDP) are detected in individuals infected by functional viruses that are genetically close related to the stop-codon lineage.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-01 11:53:02"}
• {"files"=>["https://ndownloader.figshare.com/files/973722"], "description"=>"<p>(<b>A and B</b>) Two possible routes of tDP transmission. The tDP can replicate only in dually infected individuals, so these individuals are the only source for transmission of tDP. We consider situations where a dually infected ‘donor host’ contacts a ‘recipient host’ that is either uninfected and completely susceptible (in panel A) or infected with the functional virus (DENV-1) only (in panel B). By chance, the viral population that is transmitted to the recipient host may contain the tDPs only (P), the functional virus only (Q), or both types of particles (W). If the transmitted viral population consists of only the functional virus, the recipient host would become a DENV-1-only infected individual. If this viral population consists of both types of particles, it is possible for the recipient host to become a dually infected individual, irrespective of whether the recipient host is already infected or not. However, if the transmitted viral population consists of only tDP particles, the recipient host can become dually infected only if it is already infected with DENV-1 as shown in panel B (a pathway we call super-infection). (<b>C</b>) Schematic for the compartmental model of DENV-1 and tDP transmission dynamics. S, E, I and R denote the susceptible, exposed, infectious, recovered compartments for the functional virus, respectively. G and D are the exposed and infectious compartments for dual infection, respectively. <i>σ</i> and <i>γ</i> denote the rates at which latent individuals become infectious and infectious individuals recover, respectively. Dashed lines denote processes with rates that are orders of magnitude lower than rates shown with solid lines. The mathematical expressions show the infectious population groups that contribute to each route of transmission, and associated scaling parameters. Model equations are shown in <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003193#ppat.1003193.e001\" target=\"_blank\">Eqn. (1)</a> of the <a href=\"http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003193#s4\" target=\"_blank\">Methods</a>.</p>", "links"=>[], "tags"=>["diagrams", "routes", "tdp", "compartmental", "denv-1"], "article_id"=>642006, "categories"=>["Virology", "Biological Sciences", "Microbiology", "Evolutionary Biology"], "users"=>["Ruian Ke", "John Aaskov", "Edward C. Holmes", "James O. Lloyd-Smith"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003193.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Schematic_diagrams_for_different_transmission_routes_of_tDP_and_the_compartmental_model_for_tDP_and_DENV_1_transmission_/642006", "title"=>"Schematic diagrams for different transmission routes of tDP and the compartmental model for tDP and DENV-1 transmission.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-01 11:53:54"}
• {"files"=>["https://ndownloader.figshare.com/files/973725"], "description"=>"<p>(<b>A</b>) The ratio of the cumulative number of dually infected humans (D) over the cumulative number of humans infected with DENV-1 only (I) during the 2^nd and 3^rd years after tDP emergence (corresponding to calendar year 2001 and 2002) is plotted against the parameter <i>W</i> describing the efficiency of co-transmission. (<b>B</b>) The fraction of super-infected humans among all dually infected humans for different values of the co-transmission coefficient. Simulation results where tDP is and is not transmitted persistently during the 3^rd year of the simulation are denoted as red and gray dots, respectively. Vertical dashed lines denote the threshold of <i>W</i> = 1, whereas the horizontal dashed line in panel A denotes the threshold where the number of dually infected cases is equal to the number of singly infected cases. 1,000 samples of Latin hypercube sampling were performed with parameters <i>P</i> and <i>Q</i> sampled uniformly between 0 and 1 and <i>W</i> sampled uniformly between 0 and 1.3.</p>", "links"=>[], "tags"=>["tdp", "transmitted", "co-infection", "susceptible"], "article_id"=>642009, "categories"=>["Virology", "Biological Sciences", "Microbiology", "Evolutionary Biology"], "users"=>["Ruian Ke", "John Aaskov", "Edward C. Holmes", "James O. Lloyd-Smith"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003193.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_tDP_is_primarily_transmitted_through_the_co_infection_of_susceptible_individuals_/642009", "title"=>"The tDP is primarily transmitted through the co-infection of susceptible individuals.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-01 11:54:42"}
• {"files"=>["https://ndownloader.figshare.com/files/973728"], "description"=>"<p>The y-axis shows the predicted fold increase in total DENV-1 infected humans during 2001 and 2002 relative to the number of human cases in the absence of tDP. The x-axis shows the predicted fraction of human cases who were dually infected during 2002. The color of the dots indicates the value of R_eff,co as shown in the color bar. Only simulations with R_eff,co>1 are shown; when R_eff,co<1, the fraction of dually infected humans is near 0 and the fold increase in total dengue cases is near 1. 10,000 sets of parameter values were sampled using Latin hypercube sampling. <i>P</i> and <i>Q</i> were sampled from a uniform distribution between 0 and 1 and W was sampled from a uniform distribution between 0 and 2. <i>γ_H,D</i> and <i>σ_V,D</i> were sampled in a way such that the fold changes in human infectious period (<i>γ_H,D/γ_H</i>) and mosquito incubation period (<i>σ_V,D/σ_V</i>) range from 0.5 to 2. The values of <i>γ_H</i>, <i>σ_V</i> and <i>μ_V</i> are kept constant.</p>", "links"=>[], "tags"=>["leads", "dually", "infected", "individuals"], "article_id"=>642012, "categories"=>["Virology", "Biological Sciences", "Microbiology", "Evolutionary Biology"], "users"=>["Ruian Ke", "John Aaskov", "Edward C. Holmes", "James O. Lloyd-Smith"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003193.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increasing_R_eff_co_above_1_leads_to_increases_in_the_fraction_of_dually_infected_individuals_among_all_infected_individuals_and_in_the_total_number_of_infected_individuals_/642012", "title"=>"Increasing R_eff,co above 1 leads to increases in the fraction of dually infected individuals among all infected individuals and in the total number of infected individuals.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-01 11:54:54"}
• {"files"=>["https://ndownloader.figshare.com/files/973734", "https://ndownloader.figshare.com/files/973735", "https://ndownloader.figshare.com/files/973738", "https://ndownloader.figshare.com/files/973741", "https://ndownloader.figshare.com/files/973744", "https://ndownloader.figshare.com/files/973747", "https://ndownloader.figshare.com/files/973750", "https://ndownloader.figshare.com/files/973764", "https://ndownloader.figshare.com/files/973767", "https://ndownloader.figshare.com/files/973769", "https://ndownloader.figshare.com/files/973772"], "description"=>"<div><p>Intra-host sequence data from RNA viruses have revealed the ubiquity of defective viruses in natural viral populations, sometimes at surprisingly high frequency. Although defective viruses have long been known to laboratory virologists, their relevance in clinical and epidemiological settings has not been established. The discovery of long-term transmission of a defective lineage of dengue virus type 1 (DENV-1) in Myanmar, first seen in 2001, raised important questions about the emergence of transmissible defective viruses and their role in viral epidemiology. By combining phylogenetic analyses and dynamical modeling, we investigate how evolutionary and ecological processes at the intra-host and inter-host scales shaped the emergence and spread of the defective DENV-1 lineage. We show that this lineage of defective viruses emerged between June 1998 and February 2001, and that the defective virus was transmitted primarily through co-transmission with the functional virus to uninfected individuals. We provide evidence that, surprisingly, this co-transmission route has a higher transmission potential than transmission of functional dengue viruses alone. Consequently, we predict that the defective lineage should increase overall incidence of dengue infection, which could account for the historically high dengue incidence reported in Myanmar in 2001–2002. Our results show the unappreciated potential for defective viruses to impact the epidemiology of human pathogens, possibly by modifying the virulence-transmissibility trade-off, or to emerge as circulating infections in their own right. They also demonstrate that interactions between viral variants, such as complementation, can open new pathways to viral emergence.</p> </div>", "links"=>[], "tags"=>["phylodynamic", "emergence", "epidemiological", "transmissible", "defective", "dengue", "viruses"], "article_id"=>642018, "categories"=>["Virology", "Biological Sciences", "Microbiology", "Evolutionary Biology"], "users"=>["Ruian Ke", "John Aaskov", "Edward C. Holmes", "James O. Lloyd-Smith"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003193.s001", "https://dx.doi.org/10.1371/journal.ppat.1003193.s002", "https://dx.doi.org/10.1371/journal.ppat.1003193.s003", "https://dx.doi.org/10.1371/journal.ppat.1003193.s004", "https://dx.doi.org/10.1371/journal.ppat.1003193.s005", "https://dx.doi.org/10.1371/journal.ppat.1003193.s006", "https://dx.doi.org/10.1371/journal.ppat.1003193.s007", "https://dx.doi.org/10.1371/journal.ppat.1003193.s008", "https://dx.doi.org/10.1371/journal.ppat.1003193.s009", "https://dx.doi.org/10.1371/journal.ppat.1003193.s010", "https://dx.doi.org/10.1371/journal.ppat.1003193.s011"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Phylodynamic_Analysis_of_the_Emergence_and_Epidemiological_Impact_of_Transmissible_Defective_Dengue_Viruses__/642018", "title"=>"Phylodynamic Analysis of the Emergence and Epidemiological Impact of Transmissible Defective Dengue Viruses", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-03-01 11:56:00"}
• {"files"=>["https://ndownloader.figshare.com/files/1005798"], "description"=>"*<p>95% confidence intervals that are calculated using parameter profiling.</p>**<p>The ranges of variation are calculated using the estimated parameter values at the boundaries of the 95% confidence intervals.</p>", "links"=>[], "tags"=>["estimates", "parameter", "corresponding", "denv-1", "cases", "2001"], "article_id"=>666419, "categories"=>["Virology", "Biological Sciences", "Microbiology", "Evolutionary Biology"], "users"=>["Ruian Ke", "John Aaskov", "Edward C. Holmes", "James O. Lloyd-Smith"], "doi"=>["https://dx.doi.org/10.1371/journal.ppat.1003193.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Maximum_likelihood_estimates_of_parameter_values_and_their_corresponding_increase_in_overall_DENV_1_cases_during_2001_and_2002_/666419", "title"=>"Maximum-likelihood estimates of parameter values and their corresponding increase in overall DENV-1 cases during 2001 and 2002.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-28 01:46:59"}

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Relative Metric

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F1000Prime