Role of heparan sulfate for attachment and entry of tick-borne encephalitis virus.

Attachment of the flavivirus tick-borne encephalitis (TBE) virus to different permissive cell lines was investigated by a newly established quantitative assay using fluorescence-labeled virus. Previous work had shown that BHK-21 cell-adapted mutants of TBE virus had acquired potential heparan sulfate (HS) binding sites on the outer surface of protein E. Quantitative analysis of one of these mutants indicated that it attached to HS-expressing cell lines with a 10- to 13-fold higher affinity than wild-type TBE virus strain Neudoerfl. CHO cells deficient in HS synthesis bound less than 5% of the amount of wild-type or mutant virus that could attach to HS-containing CHO cells but were nevertheless found to be highly susceptible to infection with both viruses. Thus, even though HS is a major determinant of TBE virus attachment on HS-expressing cells, our findings suggest the existence of an alternative host cell receptor that is less abundant than HS.