Measles virus-induced immunosuppression in cotton rats is associated with cell cycle retardation in uninfected lymphocytes.

Measles virus (MV)-induced immune suppression during acute measles often leads to secondary viral, bacterial and parasitic infections which severely complicate the course of disease. Previously, we have shown that cotton rats are a good animal model to study MV-induced immune suppression, where proliferation inhibition after ex vivo stimulation of cotton rat spleen cells is induced by the viral glycoproteins (fusion and haemagglutinin proteins). We have now tested a variety of putative mechanisms of MV-induced immune suppression in this animal model. Proliferation inhibition is not due to fusion mediated by the MV glycoproteins and subsequent lysis of cells. Other putative mechanisms like classical anergy (unresponsiveness towards IL-2) or apoptosis do not seem to play a role in MV-induced immune suppression. In contrast, it was shown that spleen cells from infected animals preferentially accumulate in the G0/G1 phase and progress more slowly through the cell cycle after mitogen stimulation in comparison to cells from non-infected animals. These data indicate a retardation of the cell cycle which is correlated with proliferation inhibition and might have severe consequences in mounting an effective immune response.