1. Genetic and phenotypic characterization of recently discovered enterovirus D type 111
- Author
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Marie-Line Joffret, Maël Bessaud, Ionela Gouandjika-Vasilache, Marie-Claire Endegue-Zanga, Francis Delpeyroux, Richard Njouom, Arthur Mazitchi, Serge Alain Sadeuh-Mba, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Biologie des virus entériques (BVE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur de Bangui, This project was supported by the Fondation Total (grant S-CM15010-05B), by an ACIP grant (ACIP 162-19) from Institut Pasteur Paris and by the European Virus Archive goes global project (EVAg, European Union's Horizon 2020 research and innovation programme, grant agreement No 653316). We are grateful for the financial support of the World Health Organization, The authors thank the staff of the Pasteur International Bioresources network (PIBnet), Plateforme de microbiologie mutualisée, Institut Pasteur, Paris. This work used the computational and storage services (TARS cluster) provided by the IT department at Institut Pasteur, Paris., European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), Bessaud, Maël, European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID, and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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0301 basic medicine ,RNA viruses ,Physiology ,Epidemiology ,RC955-962 ,Simian ,medicine.disease_cause ,Pathology and Laboratory Medicine ,Genetic recombination ,Biochemistry ,Enteroviruses ,Database and Informatics Methods ,0302 clinical medicine ,Immune Physiology ,Arctic medicine. Tropical medicine ,Medicine and Health Sciences ,Phylogeny ,Genetics ,Enterovirus D, Human ,[SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Immune System Proteins ,Strain (biology) ,Poliovirus ,Genomics ,3. Good health ,Infectious Diseases ,Phenotype ,Medical Microbiology ,Viral Pathogens ,Genetic Epidemiology ,Viruses ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Biological Cultures ,Pathogens ,Public aspects of medicine ,RA1-1270 ,Sequence Analysis ,Research Article ,Bioinformatics ,030231 tropical medicine ,Immunology ,Sequence Databases ,Enterovirus D ,Genome, Viral ,Biology ,Research and Analysis Methods ,Microbiology ,Antibodies ,Cell Line ,03 medical and health sciences ,Open Reading Frames ,Sequence Motif Analysis ,Virology ,medicine ,Enterovirus Infections ,Humans ,Microbial Pathogens ,Comparative genomics ,Public Health, Environmental and Occupational Health ,Organisms ,Outbreak ,Biology and Life Sciences ,Computational Biology ,Proteins ,Comparative Genomics ,Cell Cultures ,biology.organism_classification ,Viral Replication ,030104 developmental biology ,Biological Databases ,Viral replication ,Sequence Alignment - Abstract
Members of the species Enterovirus D (EV-D) remain poorly studied. The two first EV-D types (EV-D68 and EV-D70) have regularly caused outbreaks in humans since their discovery five decades ago but have been neglected until the recent occurrence of severe respiratory diseases due to EV-D68. The three other known EV-D types (EV-D94, EV-D111 and EV-D120) were discovered in the 2000s-2010s in Africa and have never been observed elsewhere. One strain of EV-D111 and all known EV-D120s were detected in stool samples of wild non-human primates, suggesting that these viruses could be zoonotic viruses. To date, EV-D111s are only known through partial genetic sequences of the few strains that have been identified so far. In an attempt to bring new pieces to the puzzle, we genetically characterized four EV-D111 strains (among the seven that have been reported until now). We observed that the EV-D111 strains from human samples and the unique simian EV-D111 strain were not phylogenetically distinct, thus suggesting a recent zoonotic transmission. We also discovered evidences of probable intertypic genetic recombination events between EV-D111s and EV-D94s. As recombination can only happen in co-infected cells, this suggests that EV-D94s and EV-D111s share common replication sites in the infected hosts. These sites could be located in the gut since the phenotypic analysis we performed showed that, contrary to EV-D68s and like EV-D94s, EV-D111s are resistant to acid pHs. We also found that EV-D111s induce strong cytopathic effects on L20B cells, a cell line routinely used to specifically detect polioviruses. An active circulation of EV-D111s among humans could then induce a high number of false-positive detection of polioviruses, which could be particularly problematic in Central Africa, where EV-D111 circulates and which is a key region for poliovirus eradication., Author summary Many examples of emergence of viruses that trigger severe diseases in humans are known. Emergence can be due to the sudden increase of the pathogenic power of a virus that had silently circulated into human populations for a long period; it can also be due to the cross-species transmission of a virus from its animal host to humans. The recent outbreaks of severe respiratory diseases due to enteroviruses D68 (EV-D68) brought to the light to potency of members of the species Enterovirus D (EV-D) to emerge as severe human pathogens. By many aspects, EV-Ds are still mysterious: their natural history and epidemiology are poorly studied and even their main hosts remain unknown. For decades, EV-Ds were believed to infect mainly humans but recent data about EV-Ds identified in sub-Saharan Africa support their zoonotic origin. In an attempt to increase our knowledge about EV-Ds, we undertook genetic and phenotypic characterization of four EV-D111 isolates, a virus type that was recently uncovered in humans and in non-human primates in Central Africa. Our results show that EV-D111s are probably enteric viruses and evolve by exchanging genetic sequences with EV-D94.
- Published
- 2019
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