In:
Journal of Virology, American Society for Microbiology, Vol. 80, No. 1 ( 2006-01), p. 119-129
Abstract:
Injury to neurons after West Nile virus (WNV) infection is believed to occur because of viral and host immune-mediated effects. Previously, we demonstrated that CD8 + T cells are required for the resolution of WNV infection in the central nervous system (CNS). CD8 + T cells can control infection by producing antiviral cytokines (e.g., gamma interferon or tumor necrosis factor alpha) or by triggering death of infected cells through perforin- or Fas ligand-dependent pathways. Here, we directly evaluated the role of perforin in controlling infection of a lineage I New York isolate of WNV in mice. A genetic deficiency of perforin molecules resulted in higher viral burden in the CNS and increased mortality after WNV infection. In the few perforin-deficient mice that survived initial challenge, viral persistence was observed in the CNS for several weeks. CD8 + T cells required perforin to control WNV infection as adoptive transfer of WNV-primed wild-type but not perforin-deficient CD8 + T cells greatly reduced infection in the brain and spinal cord and enhanced survival of CD8-deficient mice. Analogous results were obtained when wild-type or perforin-deficient CD8 + T cells were added to congenic primary cortical neuron cultures. Taken together, our data suggest that despite the risk of immunopathogenesis, CD8 + T cells use a perforin-dependent mechanism to clear WNV from infected neurons.
Type of Medium:
Online Resource
ISSN:
0022-538X
,
1098-5514
DOI:
10.1128/JVI.80.1.119-129.2006
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2006
detail.hit.zdb_id:
1495529-5
detail.hit.zdb_id:
80174-4
