CELLULAR TROPISM OF HUMAN ENTEROVIRUS D SPECIES SEROTYPES EV-94, EV-70 AND EV-68 IN VITRO – IMPLICATIONS FOR PATHOGENESIS
Résumé
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 investigated 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, granulacytic, 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.
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