In acute inflammatory demyelinating polyneuropathy (AIDP), the cause of autosensitization to peripheral neural tissue is unknown. In the immune-mediated neuropathy of chickens caused by Marek's disease virus (MDV), it is hypothesized that a primary viral infection of the Schwann cell, or a reactivated latent infection, may lead to release of peripheral nerve antigens which sensitize the host. Histopatholocally, the lesion resembles human AIDP. Thus, Marek's disease is the prototye of virus-induced, immune mediated demyelinating neuropathy. Peliminary studies in a mammalian system have begun, with infection of mouse peripheral nerve with murine cytomegalovirus (MCMV). In vitro infection of cultured (de-differentiated) mouse Schwann cells results in productive infection with cell lysis and death. Afer systemic (intraperitoneal) infection, sciatic nerve explant cultures are positive for MCMV in only 2% of the infected animals. With direct intraneural injection of virus into surgically exposed sciatic nerve, there is a permissive infection with peak infectious MCMV production at 4 to 7 days after infection. By week 4, all infectious virus is cleared from the nerve. However, latent MCMV infection of the (differentiated) Schwann cell occurs, as shown by growth of infectious virus from explant culture as late as 8 weeks after intraneural injection. The goals of the proposed study are: 1) To determine the cell type(s) involved in MCMV infection in vivo, using immunohistochemistry and electron microscopy to look at the productively infected cells, and in situ hybridization for determination of latently infected cells. 2) To study the process of in vivo reactivation, by immune suppression or by Wallerian degeneration after proximal nerve section. 3) To define the immune mechanisms in demyelination. Passive transfer with immune effector cells from spleen and lymph node or after in vitro sensitization to MCMV antigens or peripheral nerve antigens. Humoral mechanisms will be studied by passive transfer of serum from infected animals. In both cases typical lesions of inflammation and demyelination will be sought. Immunoblots will be used to define antigens and antibodies. In addition, monoclonal antibodies will be produced to further identify the antigenic determinants on demyelinating nerve as well as to serve as highly specific probes for immunohistological and ultra-structural analysis of the demyelination Schwann cell.
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