Faculty Opinions recommendation of Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication.
Year: 2017
Type: peer-review
Abstract: Members of rhinovirus C (RV-C) species are more likely to cause wheezing illnesses and asthma exacerbations compared with other rhinoviruses. The cellular receptor for these viruses was heretofore unknown. We report here that expression of human cadherin-related family member 3 (CDHR3) enables the cells normally unsusceptible to RV-C infection to support both virus binding and replication. A coding single nucleotide polymorphism (rs6967330, C529Y) was previously linked to greater cell-surface expression of CDHR3 protein, and an increased risk of wheezing illnesses and hospitalizations for childhood asthma. Compared with wild-type CDHR3, cells transfected with the CDHR3-Y529 variant had about 10-fold increases in RV-C binding and progeny yields. We developed a transduced HeLa cell line (HeLa-E8) stably expressing CDHR3-Y529 that supports RV-C propagation in vitro. Modeling of CDHR3 structure identified potential binding sites that could impact the virus surface in regions that are highly conserved among all RV-C types. Our findings identify that the asthma susceptibility gene product CDHR3 mediates RV-C entry into host cells, and suggest that rs6967330 mutation could be a risk factor for RV-C wheezing illnesses. PMID: 25848009 Funding information This work was supported by: NHLBI NIH HHS, United States Grant ID: P01 HL070831 NIAID NIH HHS, United States Grant ID: U19 AI104317 NIAID NIH HHS, United States Grant ID: U19-AI0104317 NIAID NIH HHS, United States Grant ID: T32 AI078985 NIGMS NIH HHS, United States Grant ID: T32 GM008692 NIGMS NIH HHS, United States Grant ID: T32 GM081061 More Less keyboard_arrow_down
Author: Johan Neyts
Institution: Rega Institute for Medical Research
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4256379753