Diagnosis of Cytomegalovirus in Immunocompromised Persons

Cytomegalovirus is the leading viral cause of congenital disease, often producing serious neurological deficits. CMV attacks the developing central nervous system(CNS) resulting in serious brain disorders that include microencephaly, epilepsy, deafness, microgyria, mental retardation, sensory loss, motor problems, and psychiatricdisturbances. In addition, CMV is a clinically important opportunistic virus that can lead to serious neurological disease in AIDS patients. The present applicationaddresses basic mechanisms of viral spread into the brain, and once in the brain, spread by intracellular transport or extracellular diffusion to other brain cells. The hypothesis that CMV can be spread through axonal transport will be studiedwith in vitro and in vivo models. Although CMV appears to have no absolute host cell preference in the brain, the hypothesis that CMV shows relative cellular preferenceswill be tested in living brain slices at different developmental ages. Using a mouse model of immunosuppression, parallel to AIDS, we will test the hypothesisthat cell-mediated immunity protects neurons in vivo from CMV proliferation. Neuronal activity plays an important role in establishing the correct circuitry duringbrain development. The hypothesis that early infection by CMV can generate disturbances in the electrophysiological activity of developing neurons will be tested with whole cell patch clamp recording using current and voltage clamp electrophysiology,and with calcium digital imaging, using primary mouse neuron cultures and brain slices. Virus mediated changes in intracellular ion levels, ion currents,transmitter responses, and membrane properties will be compared in CMV infected and control cells.

کلیدواژه ها:

CMV Infected ، Immunosuppression ، Immunosuppression ، Microencephaly