In acute inflammatory demyelinating neuropathy (AIDP), the cause for autosensitization to peripheral myelin is unknown, but disease onset frequently follows a viral infection or other stressful antecedent event. A primary viral infection of the Schwann cell, or a latent infection reactivated by a stressful antecedent event, may lead to release of peripheral nerve antigens which sensitize the host and lead to autoimmune neuropathy. This hypothesis probably explains the immune-mediated neuropathy of chickens caused by Marek's disease virus (MDV). AIDP cases are commonly associated with cytomegalovirus (CMV) or Epstein Barr Virus (EBV) infections, and CMV has been previously isolated from autopsy thoracic ganglia explant cultures. The three agents, MDV, EBV, and CMV are all lymphotrophic herpes viruses and share biological characteristics. In our experiments with murine CMV we observed that the dedifferentiated Schwann cell in culture is productively infected by MCMV. We have begun studies of MCMV infection of mouse sciatic nerve in-vivo to determine if the differentiated (myelinating) Schwann cell can be latently infected by MCMV. This finding would be consistent with the known outcome of MCMV infections in other cell types where the state of differentiation determines if infection is latent or productive. We found that sciatic nerve explant cultures were positive for MCMV in about 2% of systemically infected mice. Using direct intraneural injection of virus into surgically exposed mouse sciatic nerves, we observed a permissive infection with peak production of infectious MCMV at days 4 to 7 post-injection. By week 4 all infectious virus was cleared from the nerve, but we were able to demonstrate latent MCMV by explant cultures as late as 8 weeks post-infection. Our goals are to determine the cell type involved in the productive MCMV infection by immunohistochemistry and electron microscopy, and to use in-situ hybridization to determine the cell type which is latently infected. We will study the in-vivo reactivation of MCMV infection of peripheral nerve. We will perform experiments to detect autosensitization to peripheral nerve antigens which may accompany MCMV infection of the Schwann cell. The data which we will obtain from the MCMV infected peripheral nerve model will aid our understanding of human demyelination by virus-induced immune-mediated mechanisms.
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