Neurovirulence in feline immunodeficiency virus-infected neonatal cats is viral strain specific and dependent on systemic immune suppression.
Feline immunodeficiency virus (FIV) is a lentivirus that causes immune suppression and neurological disease in cats. Among animal viruses, individual viral strains have been shown to be neurovirulent, but the role of viral strain specificity among lentiviruses and its relationship to systemic immune suppression in the development of neurological disease remains uncertain. To determine the extent to which different FIV strains caused neurological disease, FIV V1CSF and Petaluma were compared in ex vivo assays and in vivo. Both viruses infected and replicated in macrophage and mixed glial cell cultures at similar levels, but V1CSF induced significantly greater neuronal death than Petaluma in a neurotoxicity assay. V1CSF-infected animals showed significant neurodevelopmental delay compared to the Petaluma-infected and uninfected animals. Magnetic resonance spectroscopy studies of frontal cortex revealed significantly reduced N-acetyl aspartate/creatine ratios in the V1CSF group compared to the other groups. Cyclosporin A treatment of Petaluma-infected animals caused neurodevelopmental delay and reduced N-acetyl aspartate/creatine ratios in the brain. Reduced CD4(+) and CD8(+) cell counts were observed in the V1CSF-infected group compared to the uninfected and Petaluma-infected groups. These findings suggest that neurodevelopmental delay and neuronal injury is FIV strain specific but that systemic immune suppression is also an important determinant of FIV-induced neurovirulence.
Power
C
C
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta T2N 4N1 Canada. power@ucalgary.ca
Buist
R
R
Johnston
J B
JB
Del Bigio
M R
MR
Ni
W
W
Dawood
M R
MR
Peeling
J
J
D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002415:Cats; D016923:Cell Death; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D016180:Lentivirus Infections / Q000209:etiology* / Q000276:immunology / Q000821:virology; D018655:Lymphocyte Count; D009682:Magnetic Resonance Spectroscopy; D009420:Nervous System / Q000254:growth & development / Q000473:pathology / Q000821:virology*; D009474:Neurons / Q000473:pathology / Q000821:virology; D011247:Pregnancy; D013045:Species Specificity; D014774:Virulence; D014779:Virus Replication
D017931:DNA Primers; D004279:DNA, Viral; D001224:Aspartic Acid; C000179:N-acetylaspartate