title: Studies of Echovirus 5 interactions with the cell surface: heparan sulfate mediates attachment to the host cell.
abstract: Infections caused by Echovirus 5 (E5), an enterovirus of the Picornaviridae family, have been associated with fever, rashes and sporadic cases of aseptic meningitis. To elucidate the receptor usage of this virus, the significance of a previously proposed integrin binding arginine-glycine-aspartic acid (RGD) motif found in the VP3 capsid protein was investigated, as well as the capacity of E5 to interact with heparan sulfate on the cell surface. Using the prototype strain E5 Noyce (E5N), an E5N mutant where the aspartic acid of the RGD motif has been substituted to a glutamic acid and clinical E5 isolates, the RGD motif of VP3 was found to be non-essential and hence not involved in integrin receptor binding. However, E5N and clinical E5 isolates interact with heparan sulfate at the cell surface, as demonstrated by virus replication inhibition assays using heparin and heparinase III, and studies of E5 interactions at the cell surface measured by real-time PCR analysis. In conclusion, E5 utilizes heparan sulfate as a cellular receptor, but the RGD motif of VP3 is not essential for E5 infectivity.
authors.affiliation: School of Natural Sciences, Linnaeus University, Smalandsgatan 24, SE-391 82 Kalmar, Sweden.
authors.forename: Stina
authors.initials: S
authors.lastname: Israelsson
authors.forename: Maria
authors.initials: M
authors.lastname: Gullberg
authors.forename: Nina
authors.initials: N
authors.lastname: Jonsson
authors.forename: Merja
authors.initials: M
authors.lastname: Roivainen
authors.forename: Kjell
authors.initials: K
authors.lastname: Edman
authors.forename: A Michael
authors.initials: AM
authors.lastname: Lindberg
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D029822:Enterovirus B, Human / Q000302:isolation & purification / Q000502:physiology*; D004769:Enterovirus Infections / Q000821:virology; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011991:Receptors, Virus / Q000378:metabolism*; D015678:Viral Structural Proteins / Q000378:metabolism*; D053585:Virus Attachment
chemical_list: D006497:Heparan Sulfate; D011991:Receptors, Virus; D015678:Viral Structural Proteins