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Immunomodulatory effect of rapamycin during MCMV infection

Rapamycin is an immunosuppresive drug commonly used in transplant patients. It specifically inhibits the intracellular kinase mTOR, crucial regulator of cell growth and proliferation. The mechanisms by which rapamycin suppresses immune response have been expanded from inhibition of T cell proliferation to blockade of dendritic cell (DC) maturation and support of Treg cells, including their de novo induction. However, it was recently shown that rapamycin has intrinsic immunostimulatory effect on the generation of memory CD8 T cells following lymphocytic choriomeningitis virus (LCMV) infection (Araki et al., 2009) suggesting that mTOR has an important role in modulating both innate and adaptive immune response. Human cytomegalovirus (HCMV), is a β-herpesvirus that infects the majority of world's population. Infection is usually asymptomatic, although in immunocompromised hosts, such as transplant recipients, it can cause severe diseases. HCMV infection was shown to activate mTOR signaling pathway, presumably to increase translation of viral proteins (Kudchodkar et al., 2004). Therefore it is not surprising that treatment with rapamycin had potent anti-cytomegalovirus effects in patients with allogeneic transplants (Demopoulos et al., 2008). Here we studied the effect of rapamycin in mouse model of cytomegalovirus infection, specifically on virus replication and antiviral immune response.

rapamycin; mTOR; MCMV

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