Journal article
Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed
The Journal of clinical investigation, Vol.118(7), pp.2448-2458
07/01/2008
DOI: 10.1172/JCI35454
PMCID: PMC2430500
PMID: 18568079
Abstract
The current model of measles virus (MV) pathogenesis implies that apical infection of airway epithelial cells precedes systemic spread. An alternative model suggests that primarily infected lymphatic cells carry MV to the basolateral surface of epithelial cells, supporting MV shedding into the airway lumen and contagion. This model predicts that a mutant MV, unable to enter cells through the unidentified epithelial cell receptor (EpR), would remain virulent but not be shed. To test this model, we identified residues of the MV attachment protein sustaining EpR-mediated cell fusion. These nonpolar or uncharged polar residues defined an area located near the binding site of the signaling lymphocytic activation molecule (SLAM), the receptor for MV on lymphatic cells. We then generated an EpR-blind virus maintaining SLAM-dependent cell entry and inoculated rhesus monkeys intranasally. Hosts infected with the selectively EpR-blind MV developed rash and anorexia while averaging slightly lower viremia than hosts infected with wild-type MV but did not shed virus in the airways. The mechanism restricting shedding was characterized using primary well-differentiated human airway epithelial cells. Wild-type MV infected columnar epithelial cells bearing tight junctions only when applied basolaterally, while the EpR-blind virus did not infect these cells. Thus, EpR is probably a basolateral protein, and infection of the airway epithelium is not essential for systemic spread and virulence of MV.
Details
- Title: Subtitle
- Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed
- Creators
- Vincent H.J Leonard - Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USAPatrick L Sinn - Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USAGregory Hodge - Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USATanner Miest - Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USAPatricia Devaux - Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USANuman Oezguen - Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USAWerner Braun - Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USAPaul B McCray - Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USAMichael B McChesney - Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USARoberto Cattaneo - Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.118(7), pp.2448-2458
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI35454
- PMID
- 18568079
- PMCID
- PMC2430500
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 07/01/2008
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984093336602771
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