title: Cellular tropism of human enterovirus D species serotypes EV-94, EV-70, and EV-68 in vitro: implications for pathogenesis.
abstract: Enterovirus 94 (EV-94) is an enterovirus serotype described recently which, together with EV-68 and EV-70, forms human enterovirus D species. This study investigates the seroprevalences of these three serotypes and their abilities to infect, replicate, and damage cell types considered to be essential for enterovirus-induced diseases. The cell types studied included human leukocyte cell lines, primary endothelial cells, and pancreatic islets. High prevalence of neutralizing antibodies against EV-68 and EV-94 was found in the Finnish population. The virus strains studied had wide leukocyte tropism. EV-94 and EV-68 were able to produce infectious progeny in leukocyte cell lines with monocytic, granulocytic, T-cell, or B-cell characteristics. EV-94 and EV-70 were capable of infecting primary human umbilical vein endothelial cells, whereas EV-68 had only marginal progeny production and did not induce cytopathic effects in these cells. Intriguingly, EV-94 was able to damage pancreatic islet β-cells, to infect, replicate, and cause necrosis in human pancreatic islets, and to induce proinflammatory and chemoattractive cytokine expression in endothelial cells. These results suggest that HEV-D viruses may be more prevalent than has been thought previously, and they provide in vitro evidence that EV-94 may be a potent pathogen and should be considered a potentially diabetogenic enterovirus type.
authors.affiliation: Intestinal Viruses Unit, Division of Health Protection, Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare (THL), Helsinki, Finland. teemu.smura@thl.fi
authors.forename: Teemu
authors.initials: T
authors.lastname: Smura
authors.forename: Petri
authors.initials: P
authors.lastname: Ylipaasto
authors.forename: Päivi
authors.initials: P
authors.lastname: Klemola
authors.forename: Svetlana
authors.initials: S
authors.lastname: Kaijalainen
authors.forename: Lauri
authors.initials: L
authors.lastname: Kyllönen
authors.forename: Valeria
authors.initials: V
authors.lastname: Sordi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Piemonti
authors.forename: Merja
authors.initials: M
authors.lastname: Roivainen
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000821:virology; D042783:Endothelial Cells / Q000821:virology*; D030016:Enterovirus D, Human / Q000145:classification / Q000472:pathogenicity*; D004769:Enterovirus Infections / Q000453:epidemiology* / Q000473:pathology / Q000821:virology; D006801:Humans; D007515:Islets of Langerhans / Q000821:virology*; D007962:Leukocytes / Q000821:virology*; D016036:Seroepidemiologic Studies; D012703:Serotyping; D013045:Species Specificity; D014471:Umbilical Veins / Q000166:cytology; D014779:Virus Replication