title: Heparan sulfates and coxsackievirus-adenovirus receptor: each one mediates coxsackievirus B3 PD infection.
abstract: Amino acid exchanges in the virus capsid protein VP1 allow the coxsackievirus B3 variant PD (CVB3 PD) to replicate in decay accelerating factor (DAF)-negative and coxsackievirus-adenovirus receptor (CAR)-negative cells. This suggests that molecules other than DAF and CAR are involved in attachment of this CVB3 variant to cell surfaces. The observation that productive infection associated with cytopathic effect occurred in Chinese hamster ovary (CHO-K1) cells, whereas heparinase-treated CHO-K1 cells, glucosaminoglycan-negative pgsA-745, heparan sulfate (HS)-negative pgsD-677, and pgsE-606 cells with significantly reduced N-sulfate expression resist CVB3 PD infection, indicates a critical role of highly sulfated HS. 2-O-sulfate-lacking pgsF-17 cells represented the cell line with minimum HS modifications susceptible for CVB3 PD. Inhibition of virus replication in CHO-K1 cells by polycationic compounds, pentosan polysulfate, lung heparin, and several intestinal but not kidney HS supported the hypothesis that CVB3 PD uses specific modified HS for entry. In addition, recombinant human hepatocyte growth factor blocked CVB3 PD infection. However, CAR also mediates CVB3 PD infection, because this CVB3 variant replicates in HS-lacking but CAR-bearing Raji cells, infection could be prevented by pretreatment of cells with CAR antibody, and HS-negative pgsD-677 cells transfected with CAR became susceptible for CVB3 PD. These results demonstrate that the amino acid substitutions in the viral capsid protein VP1 enable CVB3 PD to use specific modified HS as an entry receptor in addition to CAR.
authors.affiliation: Institute of Virology and Antiviral Therapy, Friedrich Schiller University-Jena, University Medical Center, Winzerlaer Strasse 10, D-07745 Jena, Germany.
authors.forename: A E
authors.initials: AE
authors.lastname: Zautner
authors.forename: U
authors.initials: U
authors.lastname: Körner
authors.forename: A
authors.initials: A
authors.lastname: Henke
authors.forename: C
authors.initials: C
authors.lastname: Badorff
authors.forename: M
authors.initials: M
authors.lastname: Schmidtke
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D016466:CHO Cells; D036022:Capsid Proteins / Q000737:chemistry / Q000502:physiology*; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D003384:Coxsackievirus Infections / Q000209:etiology*; D006224:Cricetinae; D029822:Enterovirus B, Human / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D019763:Heparin Lyase / Q000494:pharmacology; D006497:Heparan Sulfate / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D011991:Receptors, Virus / Q000502:physiology*; D014162:Transfection
chemical_list: D036022:Capsid Proteins; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D006493:Heparin; D019763:Heparin Lyase; D006497:Heparan Sulfate; D017228:Hepatocyte Growth Factor; D011991:Receptors, Virus; C568771:CLMP protein, human; C105941:coxsackievirus B receptor