ROLE OF VIRUS RECEPTOR-BEARING ENDOTHELIAL-CELLS OF THE BLOOD-BRAIN-BARRIER IN PREVENTING THE SPREAD OF MOUSE HEPATITIS VIRUS-A59 INTO THE CENTRAL-NERVOUS-SYSTEM

BALB/c mice develop a neurologic demyelinating disease after inoculati on of mouse hepatitis virus (MHV), strain A59, by the intracranial, bu t not by the intraperitoneal route. To determine the mechanisms that p revent virus spreading through the blood-brain barrier, we analyzed ex pression of MHVR, a glycoprotein that serves as receptor far mouse hep atitis virus on endothelial cells of cerebral blood vessels. Our resul ts indicated that MHVR was strongly expressed on the endoluminal pole of these cells, In addition, a direct virus binding assay showed that mouse hepatitis virus was able to bind endothelial cells via this rece ptor, Despite this expression of a functional viral receptor, in norma l mice infected with mouse hepatitis virus Toy the contra-peritoneal r oute, no in vivo viral replication could be detected in endothelial ce lls from the brain, contrasting with the equivalent cells from the liv er, However, shortly after i.v. administration of sodium dodecylsulfat e detergent to the mice, virus infection of some cerebral endothelial cells was detected in a few mice. As a consequence of detergent treatm ent, virus infection was able to cross the blood-brain barrier. These results suggest that the protective role of the blood-brain barrier ag ainst spreading of mouse hepatitis virus A59 into the central nervous system is determined by a specific restriction of viral entry into the endothelial cells of cerebral origin.