Regulation of gene expression in lymphocytes and antigen-presenting cells by measles virus: consequences for immunomodulation

Abstract.

Acute measles, a well known disease usually contracted during early childhood, is still the major cause of vaccine-preventable infant deaths worldwide. There are about 40 million cases of acute measles per year, with more than one million cases of infant death as a consequence of measles. These are mainly due to opportunistic infections which develop on the basis of a generalized suppression of the cellular immunity in the course and after the acute disease. Lymphopenia, a general proliferative unresponsiveness of T cells ex vivo and cytokine imbalance, are considered as major hallmarks of measles virus (MV) induced immunosuppression. These findings are compatible with modulation of T cell responses by viral interference with professional antigen-presenting cells such as dendritic cells or direct effects on T cells by suppression of survival or proliferation signals. In vitro, MV interaction causes a variety of effects on dendritic cells, including maturation and loss of their allostimulatory functions. Whether there is an additional impact on the quality of T cell responses is unknown as yet. It is clear, however, that surface interaction of lymphocytes with the MV glycoprotein complex is necessary and sufficient to induce a state of proliferative unresponsiveness in T cells. This surface contact mediated signal essentially interferes with the propagation of the interleukin 2 receptor signal by blocking the activation of the protein kinase B, also called Akt kinase, both in vitro and after experimental infection.