title: Attachment of coxsackievirus B3 variants to various cell lines: mapping of phenotypic differences to capsid protein VP1.
abstract: The coxsackievirus B3 (CVB3) strain Nancy P establishes a persistent carrier-state infection without visible cytopathic effect in primary human fibroblasts (HuFi H), whereas the derivative variant PD induces a complete lysis of the cell monolayer. To define the molecular basis of this exceptional growth property, the complete genomes of both viruses were sequenced and compared to all published sequences of CVB3. As a result, six unique amino acid substitutions in the VP1 capsid protein were observed. Via hybrid virus construction, the lytic phenotype was transferred to a nonlytic cDNA-generated CVB3. Mapping experiments indicate that the presence of amino acid residues K78, A80, A91, and I92 in VP1 is sufficient to induce "lytic" infections in HuFi H cells. Binding assays demonstrate that CVB3 Nancy P preferentially binds to the human coxsackievirus-adenovirus receptor (CAR), while PD exhibits a very weak interaction with CAR but strong binding to the decay accelerating factor (DAF). These results suggest that the mutated amino acid residues in VP1 are involved in receptor recognition/binding. Moreover, the lytic replication of CVB3 PD and the hybrid virus in various nonpermissive rodent cell lines indicates that cell surface molecules other than CAR and DAF may be involved in attachment of this variant to cell surfaces.
authors.affiliation: Institute for Virology, Medical Center at the Friedrich Schiller University, Winzerlaer Str. 10, Jena D-07745, Germany. i6scmi@pop3.uni-jena.de
authors.forename: M
authors.initials: M
authors.lastname: Schmidtke
authors.forename: H C
authors.initials: HC
authors.lastname: Selinka
authors.forename: A
authors.initials: A
authors.lastname: Heim
authors.forename: B
authors.initials: B
authors.lastname: Jahn
authors.forename: M
authors.initials: M
authors.lastname: Tonew
authors.forename: R
authors.initials: R
authors.lastname: Kandolf
authors.forename: A
authors.initials: A
authors.lastname: Stelzner
authors.forename: R
authors.initials: R
authors.lastname: Zell
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001665:Binding Sites; D018958:CD55 Antigens / Q000378:metabolism; D002213:Capsid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D006224:Cricetinae; D003588:Cytopathogenic Effect, Viral; D004252:DNA Mutational Analysis; D004274:DNA, Recombinant / Q000235:genetics; D029822:Enterovirus B, Human / Q000145:classification / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology / Q000821:virology; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D009928:Organ Specificity; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D011991:Receptors, Virus / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000906:Antibodies; D018958:CD55 Antigens; C568771:CLMP protein, human; C568772:CLMP protein, mouse; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D004274:DNA, Recombinant; D011991:Receptors, Virus