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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Watters, Kelly Ashraf, Shamaila Devries, Mark K. Palmenberg, Ann C. Griggs, Theodor F. Jackson, Daniel J. Gern, James E. Bochkov, Yury A. |
| Description | Author Affiliation: Bochkov YA ( Department of Pediatrics and yabochkov@wisc.edu.); Watters K ( Institute for Molecular Virology, University of Wisconsin-Madison, Madison, WI 53706.); Ashraf S ( Department of Pediatrics and.); Griggs TF ( Department of Pediatrics and.); Devries MK ( Department of Pediatrics and.); Jackson DJ ( Department of Pediatrics and.); Palmenberg AC ( Institute for Molecular Virology, University of Wisconsin-Madison, Madison, WI 53706.); Gern JE ( Department of Pediatrics and Department of Medicine, University of Wisconsin-Madison, Madison, WI 53792); |
| 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 17 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cadherins Membrane Proteins Models, Molecular Point Mutation Polymorphism, Single Nucleotide Rhinovirus Physiology Virus Replication Asthma Chemistry Genetics Metabolism Cells, Cultured Genetic Predisposition To Disease HeLa Cells Protein Structure, Tertiary Risk Factors Virus Internalization Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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