A VP1 mutation acquired during an enterovirus 71 disseminated infection confers heparan sulfate binding ability and modulates ex vivo tropism.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_AA8B59925F70
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A VP1 mutation acquired during an enterovirus 71 disseminated infection confers heparan sulfate binding ability and modulates ex vivo tropism.
Périodique
PLoS pathogens
Auteur(s)
Tseligka E.D., Sobo K., Stoppini L., Cagno V., Abdul F., Piuz I., Meylan P., Huang S., Constant S., Tapparel C.
ISSN
1553-7374 (Electronic)
ISSN-L
1553-7366
Statut éditorial
Publié
Date de publication
08/2018
Peer-reviewed
Oui
Volume
14
Numéro
8
Pages
e1007190
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Enterovirus 71 (EV71) causes hand, foot and mouth disease, a mild and self-limited illness that is sometimes associated with severe neurological complications. EV71 neurotropic determinants remain ill-defined to date. We previously identified a mutation in the VP1 capsid protein (L97R) that was acquired over the course of a disseminated infection in an immunocompromised host. The mutation was absent in the respiratory tract but was present in the gut (as a mixed population) and in blood and cerebrospinal fluid (as a dominant species). In this study, we demonstrated that this mutation does not alter the dependence of EV71 on the human scavenger receptor class B2 (SCARB2), while it enables the virus to bind to the heparan sulfate (HS) attachment receptor and modifies viral tropism in cell lines and in respiratory, intestinal and neural tissues. Variants with VP197L or VP197R were able to replicate to high levels in intestinal and neural tissues and, to a lesser extent, in respiratory tissues, but their preferred entry site (from the luminal or basal tissue side) differed in respiratory and intestinal tissues and correlated with HS expression levels. These data account for the viral populations sequenced from the patient's respiratory and intestinal samples and suggest that improved dissemination, resulting from an acquired ability to bind HS, rather than specific neurotropism determinants, enabled the virus to reach and infect the central nervous system. Finally, we showed that iota-carrageenan, a highly sulfated polysaccharide, efficiently blocks the replication of HS-dependent variants in cells and 2D neural cultures. Overall, the results of this study emphasize the importance of HS binding in EV71 pathogenesis and open new avenues for the development of antiviral molecules that may prevent this virus's dissemination.
Mots-clé
Animals, Capsid Proteins/genetics, Enterovirus A, Human/pathogenicity, Enterovirus A, Human/physiology, Hand, Foot and Mouth Disease/genetics, Hand, Foot and Mouth Disease/metabolism, Hand, Foot and Mouth Disease/virology, Heparitin Sulfate/metabolism, Humans, Lysosome-Associated Membrane Glycoproteins/metabolism, Mice, Mutation, Receptors, Scavenger/metabolism, Viral Tropism/genetics, Virus Replication/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/08/2018 13:34
Dernière modification de la notice
20/08/2019 15:14
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