Key result
Wild-type HRV54 uses heparan sulfate as an alternate receptor to ICAM-1, but this infection pathway is less efficient and strictly requires low endosomal pH.
HRV54 can use heparan sulfate as an alternative receptor to ICAM-1, but this noncatalytic receptor pathway requires the virus to be highly unstable at low pH for successful infection.
Hypothesis-generating for alternate receptor use in rhinoviruses; leaves open relevance to human infection and antiviral targeting.
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.
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Khan et al. (2007) studied Human Rhinovirus Type 54 Infection. Wild-type HRV54 uses heparan sulfate as an alternate receptor to ICAM-1, but this infection pathway is less efficient and strictly requires low endosomal pH.
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