Japanese encephalitis: Immunocytochemical studies of viral antigen and Inflammatory cells in fatal cases

Abstract

The distribution of virus and the composition of the mononuclear inflammatory response were studied in the brains of 7 children who died with Japanese encephalitis. Viral antigen was localized to neurons, with greatest involvement in the thalamus and brainstem. Quantitation of perivascular inflammatory responses showed a preponderance of T cells, but only 7 to 30% of these cells were T suppressor/cytotoxic cells. Inflammatory cells invading the parenchyma were predominantly macrophages with small numbers of T cells. B cells remained localized to perivascular cuffs. Viral antigen was progressively cleared in patients with survival of 6 days or more.

Production of lethal infection that resembles fatal human disease by intranasal inoculation of macaques with Japanese encephalitis virus.

“…A large number of infected Purkinje and small granule cells were observed in the cerebellum of the macaques, similar to what has been described for humans by Desai and others. 14 However, Johnson and others 12 found no infection of Purkinje cells. The cerebral cortex was less involved in the macaques but considerable antigen was localized in all levels of their spinal cords, especially the ventral horn.…”

“…The distribution of JE virus in the brains of macaques experimentally inoculated with JEV duplicates that previously reported in human disease. [12][13][14] In both, the virus distribution in the CNS was disseminated, with the greatest intensity in the thalamus and brain stem. A large number of infected Purkinje and small granule cells were observed in the cerebellum of the macaques, similar to what has been described for humans by Desai and others.…”

“…Although immunocytochemical studies of human autopsy material have been used to map the tissue distribution of viral antigen in fatal cases, [12][13][14] little is known about the antigen distribution pattern in monkeys. In our study with rhesus macaques, the heaviest staining was observed in the cerebellum, thalamus, and brainstem, explaining the observed muscle tremors, fasciculations, ataxia, depression, and profound coma.…”

Antigenic and Genetic Variations among Japanese Encephalitis Virus Strains Belonging to Genotype 1

“…Approximately half of the survivors suffer from permanent neurological and/or mental impairment due to the invasion and destruction of the cortical neurons and Purkinje cells by the virus (30,37). Several species of Culex mosquitoes are responsible for transmission of the virus to humans after the ingestion of blood meals from viremic birds or mammals.…”

Encephalitic Flaviviruses

“…Studies of neurotropism in a hamster model of St. Louis encephalitis virus infection have shown the importance of axonal transport through olfactory neurons (Monath et al, 1983), thus evading the blood brain barrier. However, postmortem studies on patients who died from Japanese encephalitis virus infection showed diffuse infection throughout the brain, indicating a hematogenous route of entry (Desai et al, 1995;Johnson et al, 1985). Infection of parenchyma may therefore result from either simple diffusion from vascular endothelial cells at sites where the integrity of the blood brain barrier has been compromised due to trauma, or through replication of the virus in the endothelial cells of brain capillaries, and release of the virus into the brain.…”