Extracellular matrix in the CNS induced by neuropathogenic viral infection

During the early phase of infection with an extremely neurovirulent murine coronavirus, cl‐2, the ER‐TR7 antigen (ERag)‐positive fibers (ERfibs) associated with laminin and collagen III show a rapid increase in expression levels in the meninges, followed by an appearance of the antigens in the ventricle and brain parenchyma. Then, cl‐2 invades the ventricle and ventricular wall along the newly assembled ERfibs after infection, using them as a pathway from the meninges, the initial site of infection. In the lymph nodes and spleen, ERag is mainly produced by fibroblastic reticular cells (FRCs), which play a key role in nursing the ERfibs to form a fibroblastic reticular network (FRN). The FRN functions as a conduit system to transfer antigens, cytokines or leukocytes in the lymphoid organs. In the brain parenchyma, astrocytes were found to produce the main components of mature ERfibs, such as collagen, laminin and ERag, which have been identified in the lymphoid organs. The producibility of these extracellular matrices (ECMs) by astrocytes was further confirmed by primary brain cultures, which disclosed the dissociation of laminin and ERag production, and the close association of ERag production with that of collagen, forming a fibrous structure. The pattern of ECM production in vitro indicated the process of forming mature ERfibs in the brain, that is, fibers made of collagen fibers and ERag are wrapped by laminin prepared as a sheet structure. In addition, the brain parenchymal cells that produce interferon β after infection in spite of their residence away from the sites of viral invasion were surrounded by ERfibs, which were closely associated with astrocytic fibers. These findings indicate that astrocytes play a central role in forming the astrocytic reticular network (ARN) in the brain parenchyma, as FRCs do to form FRN in the lymphoid organs.