Screening expressed sequence tag databases for endothelial-specific homologs to human junctional adhesion molecule (JAM) and A33-Ag, we identified a protein of 298 aa that represents the recently described vascular endothelial-JAM (VE-JAM)/JAM 2. We confirmed VE-JAM/JAM 2 expression to be restricted to the high endothelial venule of tonsil and lymph nodes, and we further expanded the localization to the endothelium of arterioles in and around inflammatory and tumor foci. In our functional characterizations of VE-JAM/JAM 2, we discovered that it can function as an adhesive ligand for the T cell line J45 and can interact with GM-CSF/IL-4-derived peripheral blood dendritic cells, circulating CD56+ NK cells, circulating CD56+CD3+ NK/T cells, and circulating CD56+CD3+CD8+ cytolytic T cells. In the course of our studies, we also isolated and characterized the functional VE-JAM/JAM 2 receptor, which, upon cloning, turned out to be a submitted sequence representing JAM 3 (accession number NP 113658). With these understandings, we have characterized a protein-interacting pair that can be important in the role of T, NK, and dendritic cell trafficking and inflammation.

Cell-cell interactions of the mucosal epithelia are important for the maintenance and establishment of epithelial barrier function. During events of inflammation, such cell-cell interactions are often disrupted, resulting in a leaky epithelial barrier, which in turn can lead to various inflammatory and infective dysfunctions. Human junctional adhesion molecule (huJAM), found on the mucosal epithelia and vascular endothelia of many major organ systems, is a membrane glycoprotein which resolves to a doublet band of approximately 40 and approximately 37 kDa under SDS-PAGE analysis, representing differentially glycosylated forms of the same protein. huJAM was localized to the lateral membrane of Caco-2 cells (a human colonic epithelial cell line) monolayers, in an area basolateral of the epithelial tight junctions (TJ). Through functional and biochemical assays, we show huJAM to be able to homotypically associate and to participate in TJ restitution after trypsin-EDTA disruption. Furthermore, we also observed a migration of huJAM expression toward areas of cell-cell contacts during events of cell adhesion and monolayer formation. These qualities makes huJAM a likely player in the regulation of cell-cell contacts and the subsequent formation of TJs.

BALB/c mice passively immunized with antibody to herpes simplex virus type 1 and challenged in the footpad with 105-7 plaque-forming units of herpes simplex virus type 1 were shown to be protected from neurological disease and death compared with control mice treated with normal serum or antibody to Sindbis virus. One hundred percent of untreated mice had virus recoverable from dorsal root ganglia by 48 h after infection. Whereas amputation of the infected limb at 48 h had no effect, antibody administration (resulting in titers of 1:8 and 1:16) was found to prevent acute neurological disease if administered no later than 48 h after infection. Antibody also restricted the extent of latent infection in the lumbosacral ganglia. The data provide strong evidence that antibody is effective in preventing spread of virus both in the peripheral nervous system and in central nervous system (spinal cord) tissue.

Neuroadapted mumps virus produces systemic infection in newborn hamsters after intraperitoneal inoculation. Virus is disseminated via a low-level viremia and appears to enter the central nervous system by passage through the choroid plexus. At such sites, choroidal and ependymal epithelial cells are productively infected and become a source for further viral spread throughout the brain parenchyma. The development of neutralizing and hemagglutination-inhibiting antibodies in serum correlates with the clearance of virus from most systemic sites. However, peristence of virus in both brain and kidney is demonstrated late in this infection.

SUMMARYResults of herpes simplex virus (HSV) isolation from a series of human postmortem trigeminal, thoracic and sacral ganglia were correlated with the HSV antibody type(s) detected in the sera by radioimmunoassay (RIA). HSV type I was isolated from trigeminal ganglia of 44 out of 9o individuals, from thoracic ganglia of I out of 25, and from sacral ganglia of I out of 68 cases. HSV type 2 was recovered from sacral ganglia of 8 out of 68 individuals. In all cases in which an HSV was isolated from ganglia and serum was available for testing, homologous, type-specific antibody was demonstrable, and in a few instances antibody to the heterologous HSV was also detected. In those individuals in which HSV type I was isolated from trigeminal ganglia and HSV type 2 from sacral ganglia, antibody to both virus types was present in the sera, indicating that simultaneous latent infections with each of the two viruses can occur, and that antibody is produced to each virus independently. Antibody to HSV type I, 2 or both types was demonstrated in 8 out of IO cases in which virus isolation attempts were negative, suggesting either a higher sensitivity of RIA for detecting HSV infection, or the presence of latent HSV at some other site in the body which was not sampled.