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The various strains of mouse hepatitis virus exhibit distinct organ tropisms. MHV-4(JHM) and MHV-3 are predominantly neurotropic and hepatotropic respectively. Studies on the mechanisms involved in organ specific infection of mouse hepatitis virus (MHV) have focused on several factors such as dose, route of administration, age and strain of experimental animals1. Another potential mechanism for regulation of tissue specific spread of virus is the ability of organ specific endothelial cells to selectively support the replication of different strains of MHV. Endothelial cells form an interface between circulating blood and organs and thus could serve as a barrier to infection by viruses. Endothelial cells are also heterogeneous in different organs and may exhibit selectivity in permitting viral entry, thus influencing their tissue tropism2.

Cerebral vascular endothelial cells are integral components of the blood-brain barrier and are believed to be an important site which can restrict infection of the central nervous system by viruses and other pathogens. A potential role of cerebral vascular endothelial cells in resisting CNS infection relates to the expression of lymphocyte-endothelial adhesion molecules which could impact on the generation of anti-viral immune reactivity.

Experimental allergic encephalomyelitis (EAE) is an organ-specific disease, mediated by T cells trafficking into the central nervous system (CNS) (1). EAE has served as a model system for the human demyelinating disease, multiple sclerosis (MS) (2). The mechanisms regulating the tissue tropism in organ-specific diseases such as MS are under intense investigation. Local antigen presentation (i.e., myelin basic protein), by blood-brain barrier-derived cells (endothelial cells, perivascular microglia, astrocytes), can contribute to a selective localization of T cells into the CNS (3). Expression of CNS-specific adhesion molecules, or localized CNS upregulation of systemic adhesion molecules, could also facilitate T cell trafficking into the CNS.

The direct induction of major histocompatibility complex coded molecules following virus infection of cerebral endothelial cells and astrocytes may play an important role in the pathogenesis of organ specific CNS disease. Mouse hepatitis virus type 4 (MHV-4)(JHM strain), a member of the Coronavirus family, causes a spectrum of disease ranging from fatal acute encephalomyelitis to demyelination in susceptible murine hosts (Bailey et al., 1949). Massa et al. , (1986, 1987a) demonstrated the ability of MHV-4 to directly induce la (class II) antigen expression on Lewis rat astrocytes in vitro. In contrast in the C57BL/6 mouse, Suzumura et al., (1986) showed that a related Coronavirus, MHV-A59, induced class I but not class II antigens on mouse astrocytes and oligodendrocytes.

The central thesis that we have developed (1, 2) is that not all capillary endothelial cells are alike, and that differences between these cells are reflections of their diverse embryological origins. The experimental approach for examining this thesis in our laboratory is an immunological one, made on the assumption that the endothelial cell differences of major developmental interest will be those that are expressed by differentiation antigens associated with the cell surface.