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Extensive immune-mediated hippocampal damage in mice surviving infection with neuroadapted Sindbis virus.

Abstract：

:Viral infections of the central nervous system and immune responses to these infections cause a variety of neurological diseases. Infection of weanling mice with Sindbis virus causes acute nonfatal encephalomyelitis followed by clearance of infectious virus, but persistence of viral RNA. Infection with a neuroadapted strain of Sindbis virus (NSV) causes fatal encephalomyelitis, but passive transfer of immune serum after infection protects from fatal disease and infectious virus is cleared. To determine whether persistent NSV RNA is associated with neurological damage, we examined the brains of recovered mice and found progressive loss of the hippocampal gyrus, adjacent white matter, and deep cerebral cortex associated with mononuclear cell infiltration. Mice deficient in CD4(+) T cells showed less tissue loss, while mice lacking CD8(+) T cells showed lesions comparable to those in immunocompetent mice. Mice deficient in both CD4(+) and CD8(+) T cells developed severe tissue loss similar to immunocompetent mice and this was associated with extensive infiltration of macrophages. The number of CD4(+) cells and macrophage/microglial cells, but not CD8(+) cells, infiltrating the hippocampal gyrus was correlated with the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling positive pyramidal neurons. These results suggest that CD4(+) T cells can promote progressive neuronal death and tissue injury, despite clearance of infectious virus.

journal_name

Virology

journal_title

Virology

authors

Kimura T,Griffin DE

doi

10.1016/s0042-6822(03)00110-7

subject

Has Abstract

pub_date

2003-06-20 00:00:00

pages

28-39

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042682203001107

journal_volume

311

pub_type

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