Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed

Vincent H J Leonard, Patrick L. Sinn, Gregory Hodge, Tanner Miest, Patricia Devaux, Numan Oezguen, Werner Braun, Paul B. McCray, Michael B. McChesney, Roberto Cattaneo

Research output: Contribution to journalArticle

165 Citations (Scopus)

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 baso-laterally, 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.

Original languageEnglish (US)
Pages (from-to)2448-2458
Number of pages11
JournalJournal of Clinical Investigation
Volume118
Issue number7
DOIs
StatePublished - Jul 1 2008

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Measles virus
Macaca mulatta
Epithelium
Epithelial Cells
Virus Receptors
Virus Shedding
Virus Attachment
Cell Fusion
Tight Junctions
Viremia
Anorexia
Infection
Exanthema
Virulence
Proteins
Binding Sites
Viruses

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed. / Leonard, Vincent H J; Sinn, Patrick L.; Hodge, Gregory; Miest, Tanner; Devaux, Patricia; Oezguen, Numan; Braun, Werner; McCray, Paul B.; McChesney, Michael B.; Cattaneo, Roberto.

In: Journal of Clinical Investigation, Vol. 118, No. 7, 01.07.2008, p. 2448-2458.

Research output: Contribution to journalArticle

Leonard, VHJ, Sinn, PL, Hodge, G, Miest, T, Devaux, P, Oezguen, N, Braun, W, McCray, PB, McChesney, MB & Cattaneo, R 2008, 'Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed', Journal of Clinical Investigation, vol. 118, no. 7, pp. 2448-2458. https://doi.org/10.1172/JC135454
Leonard, Vincent H J ; Sinn, Patrick L. ; Hodge, Gregory ; Miest, Tanner ; Devaux, Patricia ; Oezguen, Numan ; Braun, Werner ; McCray, Paul B. ; McChesney, Michael B. ; Cattaneo, Roberto. / Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed. In: Journal of Clinical Investigation. 2008 ; Vol. 118, No. 7. pp. 2448-2458.
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