1. Viral evolution sustains a dengue outbreak of enhanced severity
- Author
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Anavaj Sakuntabhai, Myrielle Dupont-Rouzeyrol, Etienne Simon-Loriere, Marie-Amélie Goujart, Sylvie Laumond, Antoine Biron, Ingrid Marois, Arnaud Tarantola, Ann-Claire Gourinat, Elodie Descloux, Catherine Inizan, Marine Minier, Carole Forfait, Matthieu Prot, Olivia O’Connor, Dengue et Arbovirose (URE-DA), Institut Pasteur de Nouvelle-Calédonie, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris], Direction des affaires sanitaires et sociales de Nouvelle-Calédonie, Centre hospitalier territorial Gaston-Bourret [Dumbea] (CHT), Centre hospitalier territorial Gaston-Bourret [Nouméa], Génétique fonctionnelle des maladies infectieuses - Functional Genetics of Infectious Diseases, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Génomique évolutive, modélisation et santé (CNRS-UMR2000), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Epidemiology - Epidémiologie [Nouméa, Nouvelle-Calédonie], The current work was supported by an internal seed-funding from the Institut Pasteur in New Caledonia as well as the Arbo-VIRTUESS project funded by the Actions Concertées Interpasteuriennes (project number ACIP 2014-053). ESL acknowledges funding from the French Agence Nationale de la Recherche (INCEPTION program, Investissements d'Avenir grant ANR-16-CONV-0005). This study has received funding from the French Agence Nationale de la Recherche, Investissement d'Avenir program for the Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant n°ANR-10-LABX-62-IBEID)., We warmly thank the Clinical Research Department of the Centre for Translational Research at Institut Pasteur in Paris for their support in ethic procedures. We thank Fabiana Gámbaro and Deborah Delaune for their contribution to whole-genome sequencing. We thank Ludivine Grzelak for her support in the implementation of in vitro replication kinetics., ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Génomique évolutive, modélisation et santé (GEMS)
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0301 basic medicine ,Epidemiology ,viruses ,Virus Replication ,Severity of Illness Index ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,Disease Outbreaks ,Dengue fever ,Dengue ,Drug Discovery ,hepatitis ,Phylogeny ,Severe dengue ,General Medicine ,3. Good health ,Infectious Diseases ,[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology ,whole-genome sequencing ,Viral evolution ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,RNA, Viral ,Research Article ,Genotype ,030106 microbiology ,Immunology ,viral fitness ,Genome, Viral ,Biology ,Microbiology ,Cell Line ,Evolution, Molecular ,03 medical and health sciences ,New Caledonia ,Virology ,medicine ,Animals ,Humans ,Hepatitis ,Whole Genome Sequencing ,Sequence Analysis, RNA ,Genetic Variation ,Outbreak ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Dengue Virus ,medicine.disease ,Dengue outbreak ,030104 developmental biology ,Amino Acid Substitution ,Mutation ,Viral fitness ,Parasitology - Abstract
Compared to the previous 2013–2014 outbreak, dengue 2016–2017 outbreak in New Caledonia was characterized by an increased number of severe forms associated with hepatic presentations. In this study, we assessed the virological factors associated with this enhanced severity. Whole-genome sequences were retrieved from dengue virus (DENV)-1 strains collected in 2013–2014 and from severe and non-severe patients in 2016–2017. Fitness, hepatic tropism and cytopathogenicity of DENV 2016–2017 strains were compared to those of 2013–2014 strains using replication kinetics in the human hepatic cell line HuH7. Whole-genome sequencing identified four amino acid substitutions specific to 2016–2017 strains and absent from 2013–2014 strains. Three of these mutations occurred in predicted T cell epitopes, among which one was also a B cell epitope. Strains retrieved from severe forms did not exhibit specific genetic features. DENV strains from 2016–2017 exhibited a trend towards reduced replicative fitness and cytopathogenicity in vitro compared to strains from 2013–2014. Overall, the 2016–2017 dengue outbreak in New Caledonia was associated with a viral genetic evolution which had limited impact on DENV hepatic tropism and cytopathogenicity. These mutations, however, may have modified DENV strains antigenicity, altering the anti-DENV immune response in some patients, in turn favoring the development of severe forms. Trial registration: ClinicalTrials.gov identifier: NCT04615364.
- Published
- 2021
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