Valine/isoleucine variants drive selective pressure in the VP1 sequence of EV-A71 enteroviruses
2017
Duy, Nghia Ngu | Huong, Le Thi Thanh | Ravel, Patrice | Huong, Le Thi Song | Dwivedi, Ankit | Sessions, October Michael | Hou, Yan’an | Chua, Robert | Kister, Guilhem | Afelt, Aneta | Moulia, Catherine | Gubler, Duane, J | Thiem, Vu Dinh | Thanh, Nguyen Thi Hien | Devaux, Christian | Duong, Tran Nhu | Hien, Nguyen Tran | Cornillot, Emmanuel | Gavotte, Laurent | Frutos, Roger | National Institute of Hygiene and Epidemiology / Institut National d'Hygiène et d'Épidémiologie [Hanoi, Vietnam] (NIHE) ; Pasteur Network (Réseau International des Instituts Pasteur) | Institut des Sciences de l'Evolution de Montpellier (UMR ISEM) ; Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École Pratique des Hautes Études (EPHE) ; Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS) | Interactions hôtes-vecteurs-parasites-environnement dans les maladies tropicales négligées dues aux trypanosomatides (UMR INTERTRYP) ; Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Université de Bordeaux (UB) | Ernst-Moritz-Arndt-Universität Greifswald | Centre de Biochimie Structurale [Montpellier] (CBS) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) | Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM) ; CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM) | Dpt of virology [Hai Phong] ; Viet Tiep Hospital [Hai Phong, Vietnam] | Institut de Biologie Computationnelle (IBC) ; Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) | National University of Singapore (NUS) | Uniwersytet Warszawski [Polska] = University of Warsaw [Poland] = Université de Varsovie [Pologne] (UW) | Hanoï Medical University | Infections rétrovirales et signalisation cellulaire (IRSC) ; Université Montpellier 1 (UM1)-Centre National de la Recherche Scientifique (CNRS) | Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD) ; Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM) | RIKEN Center for Life Science Technologies (RIKEN CLST) ; RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN) | The work was supported by internal grants from NIHE and from DUKE/NUS for sequencing. NDN was in part supported by European Erasmus Mundus project MAHEVA and by the PEPS project MoDyCa from University of Montpellier and CNRS.
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Show more [+] Less [-]English. BACKGROUND:In 2011-2012, Northern Vietnam experienced its first large scale hand foot and mouth disease (HFMD) epidemic. In 2011, a major HFMD epidemic was also reported in South Vietnam with fatal cases. This 2011-2012 outbreak was the first one to occur in North Vietnam providing grounds to study the etiology, origin and dynamic of the disease. We report here the analysis of the VP1 gene of strains isolated throughout North Vietnam during the 2011-2012 outbreak and before.METHODS:The VP1 gene of 106 EV-A71 isolates from North Vietnam and 2 from Central Vietnam were sequenced. Sequence alignments were analyzed at the nucleic acid and protein level. Gene polymorphism was also analyzed. A Factorial Correspondence Analysis was performed to correlate amino acid mutations with clinical parameters.RESULTS:The sequences were distributed into four phylogenetic clusters. Three clusters corresponded to the subgenogroup C4 and the last one corresponded to the subgenogroup C5. Each cluster displayed different polymorphism characteristics. Proteins were highly conserved but three sites bearing only Isoleucine (I) or Valine (V) were characterized. The isoleucine/valine variability matched the clusters. Spatiotemporal analysis of the I/V variants showed that all variants which emerged in 2011 and then in 2012 were not the same but were all present in the region prior to the 2011-2012 outbreak. Some correlation was found between certain I/V variants and ethnicity and severity.CONCLUSIONS:The 2011-2012 outbreak was not caused by an exogenous strain coming from South Vietnam or elsewhere but by strains already present and circulating at low level in North Vietnam. However, what triggered the outbreak remains unclear. A selective pressure is applied on I/V variants which matches the genetic clusters. I/V variants were shown on other viruses to correlate with pathogenicity. This should be investigated in EV-A71. I/V variants are an easy and efficient way to survey and identify circulating EV-A71 strains.
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