title: Role of Heparan Sulfate in Cellular Infection of Integrin-Binding Coxsackievirus A9 and Human Parechovirus 1 Isolates.
abstract: Heparan sulfate/heparin class of proteoglycans (HSPG) have been shown to function in cellular attachment and infection of numerous viruses including picornaviruses. Coxsackievirus A9 (CV-A9) and human parechovirus 1 (HPeV-1) are integrin-binding members in the family Picornaviridae. CV-A9 Griggs and HPeV-1 Harris (prototype) strains have been reported not to bind to heparin, but it was recently shown that some CV-A9 isolates interact with heparin in vitro via VP1 protein with a specific T132R/K mutation. We found that the infectivity of both CV-A9 Griggs and HPeV-1 Harris was reduced by sodium chlorate and heparinase suggestive of HSPG interactions. We analyzed the T132 site in fifty-four (54) CV-A9 clinical isolates and found that only one of them possessed T132/R mutation while the other nine (9) had T132K. We then treated CV-A9 Griggs and HPeV-1 Harris and eight CV-A9 and six HPeV-1 clinical isolates with heparin and protamine. Although infectivity of Griggs strain was slightly reduced (by 25%), heparin treatment did not affect the infectivity of the CV-A9 isolates that do not possess the T132R/K mutation, which is in line with the previous findings. Some of the HPeV-1 isolates were also affected by heparin treatment, which suggested that there may be a specific heparin binding site in HPeV-1. In contrast, protamine (a specific inhibitor of heparin) completely inhibited the infection of both prototypes and clinical CV-A9 and HPeV-1 isolates. We conclude that T132R/K mutation has a role in heparin binding of CV-A9, but we also show data, which suggest that there are other HSPG binding sites in CV-A9. In all, we suggest that HSPGs play a general role in both CV-A9 and HPeV-1 infections.
authors.affiliation: Department of Virology, University of Turku, Turku, Finland.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Merilahti
authors.affiliation: Department of Virology, University of Turku, Turku, Finland.|Department of Medical microbiology, Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Eveliina
authors.initials: E
authors.lastname: Karelehto
authors.affiliation: Department of Virology, University of Turku, Turku, Finland.|Biomaterials and Diagnostics Group, Turku University of Applied Sciences, Turku, Finland.
authors.forename: Petri
authors.initials: P
authors.lastname: Susi
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003384:Coxsackievirus Infections / Q000378:metabolism / Q000821:virology*; D029822:Enterovirus B, Human / Q000302:isolation & purification*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics; D030061:Parechovirus / Q000302:isolation & purification*; D010850:Picornaviridae Infections / Q000378:metabolism / Q000821:virology*; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000378:metabolism; D000099058:Exostosin 1
chemical_list: D006497:Heparan Sulfate; D016023:Integrins; D017351:N-Acetylglucosaminyltransferases; D014764:Viral Proteins; D000099058:Exostosin 1