Experimental encephalitis following peripheral inoculation of West Nile virus in mice of different ages

Abstract

SUMMARYExperimental arbovirus infections of mice provide a convenient model to study factors which determine the occurrence or severity of encephalitis following extraneural infection with certain neurotropic viruses. Varying doses of West Nile or Powassan viruses were inoculated by intraperitoneal or intramuscular routes into mice of varing ages; individual variables were manipulated to influence the outcome of infection. Three patterns of pathogenesis were delineated: (1) Fatal encephalitis, preceded by early viraemia, and invasion of the central nervous system. (2) Inapparent infection, with no detectable viraemia and no evidence of central nervous system invasion. (3) Subelinical encephalitis, usually preceded by trace viraemia, with minimal transient levels of virus in the brain. In this latter type of subelinical infection with a potentially lethal virus, the immune response probably plays an important role in recovery.

CD8+T Cells Mediate Recovery andImmunopathology in West Nile VirusEncephalitis

“…Many strains of WNV are neuroinvasive and can induce fatal encephalitis in mice and humans (18,52,58). In the present study, we investigated the mouse-virulent Sarafend strain of WNV as a model of WNV-induced encephalitis.…”

Pathobiology of the Flaviviruses

“…2) (Albrecht, 1968;Nathanson, 1980). Three patterns of pathogenesis have been defined (Weiner et al, 1970;Nathanson, 1980): (1) fatal encephalitis usually preceded by early viremia and extensive extraneural replication; (2) subclinical encephalitis, usually preceded by low viremia, late establishment of brain infection, and clearance with minimal destructive pathology; and (3) inapparent infection, with trace viremia, limited extraneural replication, and no neuroinvasion. The role of immune responses in limiting viral dissemination has been repeatedly demonstrated in experiments employing immunosuppressive agents, which can convert subclinical to lethal encephalitis.…”

“…Studies of experimental flavivirus encephalitis in mice have shown a relationship among level of viremia, development of brain infection (Weiner et al, 1970), and widespread or multisite simultaneous appearance of viral antigen in nervous tissue (Albrecht, 1960), supporting the concept of hematogenous spread to the CNS (Johnson, 1982). The process by which flavivirus particles cross the blood-brain barrier remains uncertain.…”

Lethal Encephalitis in 14-Day-Old Mice Given Avirulent Semliki Forest Virus

“…Other workers have found that high doses of West Nile virus produced a readily apparent encephalitis with patchy neuronal necrosis, particularly in the cerebral cortex and hippocampus. whereas in a subclinical infection the encephalitis was mild [ 19). A single dose of cyclophosphamide 24 hours after intraperitoneal infection of 10" LD,,, of West Nile virus converted an inapparent mouse brain infection into a lethal infection [4].…”