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

• DOI: 10.1371/journal.ppat.1007190
• Publication Date: 2018-08-03T20:01:27Z
• Authors: Eirini D. Tseligka; Komla Sobo; Luc Stoppini; Valeria Cagno; Fabien Abdul; Isabelle Piuz; Pascal Meylan; Song Huang; Samuel Constant; Caroline Tapparel
• Keywords: Ex vivo; Enterovirus 71; Tissue tropism

Enterovirus 71 (EV71) causes hand, foot and mouth disease, a mild self-limited illness that is sometimes associated with severe neurological complications. EV71 neurotropic determinants remain ill-defined to date. We previously identified mutation in the VP1 capsid protein (L97R) was acquired over course of disseminated infection an immunocompromised host. The absent respiratory tract but present gut (as mixed population) blood cerebrospinal fluid dominant species). In this study, we demonstrated does not alter dependence on human scavenger receptor class B2 (SCARB2), while it enables virus bind heparan sulfate (HS) attachment modifies viral tropism cell lines respiratory, intestinal neural tissues. Variants VP197L or VP197R were able replicate high levels tissues and, lesser extent, tissues, their preferred entry site (from luminal basal tissue side) differed correlated HS expression levels. These data account for populations sequenced from patient's samples suggest improved dissemination, resulting ability HS, rather than specific neurotropism determinants, enabled reach infect central nervous system. Finally, showed iota-carrageenan, highly sulfated polysaccharide, efficiently blocks replication HS-dependent variants cells 2D cultures. Overall, results study emphasize importance binding pathogenesis open new avenues development antiviral molecules may prevent virus's dissemination.