Human rhinovirus type 54 infection via heparan sulfate is less efficient and strictly dependent on low endosomal pH.
K-type major-group human rhinoviruses (HRVs) (including HRV54) share a prominent lysine residue in the HI surface loop of VP1 with all minor-group HRVs. Despite the presence of this residue, they cannot use members of the low-density lipoprotein receptor family for productive infection. Reexamining all K-type viruses for receptor usage, we noticed that HRV54 is able to replicate in RD cells that lack the major-group receptor intercellular adhesion molecule 1 (ICAM-1). By using receptor blocking assays, inhibition of sulfation, enzymatic digestion, and proteoglycan-deficient cell lines, we show here that wild-type HRV54, without any adaptation, uses heparan sulfate (HS) proteoglycan as an alternate receptor. However, infection via HS is less efficient than infection via ICAM-1. Moreover, HRV54 has an acid lability profile similar to that of the minor-group virus HRV2. In ICAM-1-deficient cells its replication is completely blocked by the H(+)-ATPase inhibitor bafilomycin A1, whereas in ICAM-1-expressing cells it replicates in the presence of the drug. Thus, use of a "noncatalytic" receptor requires the virus to be highly unstable at low pH.
Khan
Abdul Ghafoor
AG
Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna, A-1030 Vienna, Austria.
Pichler
Johannes
J
Rosemann
Anke
A
Blaas
Dieter
D
D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D018942:Macrolides / Q000633:toxicity; D010850:Picornaviridae Infections / Q000378:metabolism*; D012229:Rhinovirus / Q000378:metabolism*; D053585:Virus Attachment; D014779:Virus Replication / Q000187:drug effects
D019812:Heparan Sulfate Proteoglycans; D018942:Macrolides; D018799:Intercellular Adhesion Molecule-1; C040929:bafilomycin A1