Human rhinovirus type 89 variants use heparan sulfate proteoglycan for cell attachment.
We have previously isolated mutants of the major-group human rhinovirus type 89 that grow in cells deficient in intercellular adhesion molecule 1 (ICAM-1), the receptor used by the wild-type virus for cell entry [A. Reischl, M. Reithmayer, G. Winsauer, R. Moser, I. Goesler, and D. Blaas., J. Virol. 75:9312-9319, 2001]. We now demonstrate that one of these variants utilizes heparan sulfate proteoglycan (HSPG) as a cellular receptor. Adaptation to ICAM-1-deficient cells not only resulted in the newly acquired receptor specificity but also rendered the virus less stable at low pH and at elevated temperatures. This instability might compensate for the absence of the uncoating activity of ICAM-1. Whereas wild-type virus infection via ICAM-1 proceeded in the presence of the vesicular H(+)-ATPase inhibitor bafilomycin A1, infection by the mutant via HSPG was prevented by the drug. This suggests that the low pH prevailing in endosomal compartments is required for uncoating in the absence of the catalytic activity of ICAM-1.
Vlasak
Markete
M
Max F. Perutz Laboratories, University Departments at the Vienna Biocenter, Department of Medical Biochemistry, Medical University of Vienna, Dr. Bohr Gasse 9/3, A-1030 Vienna, Austria.
Goesler
Irene
I
Blaas
Dieter
D
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D010850:Picornaviridae Infections / Q000821:virology*; D012229:Rhinovirus / Q000502:physiology*; D013696:Temperature; D014779:Virus Replication
D019812:Heparan Sulfate Proteoglycans; D018799:Intercellular Adhesion Molecule-1