Article

Neurovirulence depends on virus input titer in brain in feline immunodeficiency virus infection: evidence for activation of innate immunity and neuronal injury.

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
Journal of NeuroVirology (impact factor: 2.31). 10/2002; 8(5):420-31. DOI:10.1080/13550280260422721 pp.420-31
Source: PubMed

ABSTRACT Lentiruses cause neurological disease depending on the virus strain and its neurotropism, yet it remains uncertain to what the impact of infectious virus quantity in the brain early in infection is on the subsequent development of neurological disease or neurovirulence. We investigated the relationship between infectious virus input titer and the resulting neurovirulence, using ex vivo and in vivo assays of feline immunodeficiency virus (FIV)-induced neurovirulence. FIV infection of cell cultures and neonatal cats was performed using 10(2.5) (low-titer) or 10(4.5) (high-titer) 50% tissue culture infectious doses (TCID(50))/ml of the neurovirulent FIV strain, V1CSF. Ex vivo neurotoxicity assays revealed that conditioned medium (CM) from feline macrophages infected with high-titer (P <.001) or low-titer (P <.01) V1CSF induced greater neuronal death than CM from mock-infected cells. In vivo, animals infected intracranially with high-titer V1CSF showed neurodevelopmental delays compared to mock-infected animals (P <.001) and animals infected with low-titer V1CSF (P <.02), concurrent with reduced weight gains and greater depletion of CD4+ cells over a 12-week period. Neuropathological changes, including astrogliosis, macrophage activation, and neuronal damage, were evident in V1CSF-infected animals and were viral titer dependent. In vivo magnetic resonance (MR) spectroscopy and proton nuclear magnetic resonance ((1)H-NMR) spectroscopy of tissue extracts revealed evidence of neuronal injury, including reduced N-acetyl aspartate/creatine (P <.05) and increased trimethylamine/creatine (P <.05) ratios, in the frontal cortex of high-titer V1CSF-infected animals compared to the other groups. T2-weighted MR imaging detected increased signal intensities in the frontal cortex and white matter of V1CSF-infected animals relative to controls, which was more evident as viral titer increased (P <.01). The present findings indicate that lentivirus infectious titers in the brain during the early stages of infection determine the severity of neurovirulence, reflected by neurobehavioral deficits, together with neuroradiological and neuropathological findings of activation of innate immunity and neuronal injury.

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    Article: Lentivirus infection causes neuroinflammation and neuronal injury in dorsal root ganglia: pathogenic effects of STAT-1 and inducible nitric oxide synthase.
    Yu Zhu, Gareth Jones, Shigeki Tsutsui, Wycliffe Opii, Shuhong Liu, Claudia Silva, D Allan Butterfield, Christopher Power
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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

CD4+ cells
 
cell cultures
 
conditioned medium
 
ex vivo
 
feline immunodeficiency virus
 
FIV)-induced neurovirulence
 
frontal cortex
 
high-titer V1CSF-infected animals
 
infectious virus input titer
 
lentivirus infectious titers
 
mock-infected cells
 
neuronal injury
 
neurovirulent FIV strain
 
proton nuclear magnetic resonance
 
resulting neurovirulence
 
subsequent development
 
V1CSF-infected animals
 
viral titer
 
virus strain
 
vivo magnetic resonance