THE PATHOGENESIS OF HERPES VIRUS ENCEPHALITIS. I. VIRUS PATHWAYS TO THE NERVOUS SYSTEM OF SUCKLING MICE DEMONSTRATED BY FLUORESCENT ANTIBODY STAINING.
The pathogenesis of herpes simplex virus encephalitis and myelitis was studied in suckling mice using routine titration procedures and fluorescent antibody staining for the identification of infected cells. After intracerebral inoculation virus was shown to disperse rapidly in the cerebrospinal fluid (CSF), multiply in meninges and ependyma, and then invade the underlying parenchyma infecting both neurons and glia. Following extraneural inoculation virus gained access to the central nervous system (CNS) by both hematogenous and neural pathways. After intraperitoneal and intranasal inoculation virus was found to multiply in viscera and produce viremia; foci of CNS infection then developed around small cerebral vessels. After subcutaneous and intranasal inoculation neural spread of virus was demonstrated along corresponding peripheral and cranial nerves. This spread resulted from the centripetal infection of endoneural cells (Schwann cells and fibroblasts). Antigen was not found in axons even after infection of the corresponding ganglion cell perikaryon. Subsequent spread within the CNS was unrelated to neural tracts, and there was no evidence of axonal spread of virus in the host-virus system studied. These findings are discussed in relation to previous and current theories of the viral "blood-brain barrier" and neural pathways of infection.
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies; D000941:Antigens; D001812:Blood-Brain Barrier; D001921:Brain; D004660:Encephalitis; D020803:Encephalitis, Herpes Simplex; D005004:Ethmoid Bone; D005453:Fluorescence; D005455:Fluorescent Antibody Technique; D006561:Herpes Simplex; D006566:Herpesviridae Infections; D007136:Immunoglobulins; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008032:Limbic System; D008578:Meninges; D051379:Mice; D008853:Microscopy; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D012106:Research; D018139:Simplexvirus; D013116:Spinal Cord; D013194:Staining and Labeling; D014276:Trigeminal Nerve
D000906:Antibodies; D000941:Antigens; D007136:Immunoglobulins
ANIMALS, NEWBORN; BLOOD-BRAIN BARRIER; ENCEPHALITIS; ETHMOID BONE; EXPERIMENTAL LAB STUDY; FLUORESCENT ANTIBODY TECHNIC; HERPES SIMPLEX; INJECTIONS, INTRAPERITONEAL; INJECTIONS, SUBCUTANEOUS; LIMBIC SYSTEM; MICE; MICROSCOPY, FLUORESCENCE; MICROSCOPY, PHASE CONTRAST; SPINAL CORD; TRIGEMINAL NERVE