Measles virus infection induces terminal differentiation of human thymic epithelial cells

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 me asles virus infection in vitro, resulting in infectious viral particle prod uction and syncytium formation. Measles virus inhibits thymic epithelial ce ll growth and induces an arrest in the G(0)/G(1) phases of the cell cycle. Moreover, we show that measles virus induces a progressive thymic epithelia l 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 characteri zed by morphological and phenotypic changes. Measles virus-infected attache d cells present fusiform and stellate shapes followed by a loss of cell-cel l contacts and a shift from low- to high-molecular-weight keratin expressio n. Measles virus infection induces thymic epithelial cell apoptosis in term inally differentiated cells, revealed by the condensation and degradation o f DNA in measles virus-infected floating thymic epithelial cells. Because t hymic epithelial cells are required for the generation of immunocompetent T lymphocytes, our results suggest that measles virus-induced terminal diffe rentiation of thymic epithelial cells may contribute to immunosuppression, particularly in children, in whom the thymic microenvironment is of critica l importance for the development and maturation of a functional immune syst em.