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Journal of Virology, March 1999, p. 2212-2221, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Measles Virus Infection Induces Terminal Differentiation of Human Thymic Epithelial Cells

Hélène Valentin,1,* Olga Azocar,1 Branka Horvat,1 Rejane Williems,2 Robert Garrone,2 Alexei Evlashev,1,3 Maria L. Toribio,4 and Chantal Rabourdin-Combe1

Laboratoire d'Immunobiologie Fondamentale et Clinique, INSERM U503, ENS de Lyon, 69364 Lyon Cedex 07,1 and Institut de Biologie et Chimie des Protéines, UPR 412-CNRS, 69367 Lyon Cedex 07,2 France; Institute of Experimental Medicine, RAMS, 197376 Saint Petersburg, Russia3; and Centro de Biológica Molecular Severo Ochoa, Universidad Autónoma de Madrid, Facultad de Ciencias, Campus de Cantoblanco, 28049 Madrid, Spain4

Received 3 August 1998/Accepted 7 December 1998

Measles virus infection induces a profound immunosuppression that may lead to serious secondary infections and mortality. In this report, we show that the human cortical thymic epithelial cell line is highly susceptible to measles virus infection in vitro, resulting in infectious viral particle production and syncytium formation. Measles virus inhibits thymic epithelial cell growth and induces an arrest in the G0/G1 phases of the cell cycle. Moreover, we show that measles virus induces a progressive thymic epithelial cell differentiation process: attached measles virus-infected epithelial cells correspond to an intermediate state of differentiation while floating cells, recovered from cell culture supernatants, are fully differentiated. Measles virus-induced thymic epithelial cell differentiation is characterized by morphological and phenotypic changes. Measles virus-infected attached cells present fusiform and stellate shapes followed by a loss of cell-cell contacts and a shift from low- to high-molecular-weight keratin expression. Measles virus infection induces thymic epithelial cell apoptosis in terminally differentiated cells, revealed by the condensation and degradation of DNA in measles virus-infected floating thymic epithelial cells. Because thymic epithelial cells are required for the generation of immunocompetent T lymphocytes, our results suggest that measles virus-induced terminal differentiation of thymic epithelial cells may contribute to immunosuppression, particularly in children, in whom the thymic microenvironment is of critical importance for the development and maturation of a functional immune system.

* Corresponding author. Mailing address: Laboratoire d'Immunobiologie Fondamentale et Clinique, INSERM U503, ENS de Lyon, 46, Allée d'Italie, 69364 Lyon Cedex 07, France. Phone: (33) 4 72 72 80 13. Fax: (33) 4 72 72 86 69. E-mail: Helene.Valentin{at}ens-lyon.fr.

Journal of Virology, March 1999, p. 2212-2221, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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