Neurobehavioral performance in feline immunodeficiency virus infection: integrated analysis of viral burden, neuroinflammation, and neuronal injury in cortex.
Human immunodeficiency virus (HIV) infection causes motor and neurocognitive abnormalities affecting >50% of children and 20% of adults with HIV/AIDS (acquired immunodeficiency syndrome). The closely related lentivirus, feline immunodeficiency virus (FIV), also causes neurobehavioral deficits. Herein, we investigated the extent to which FIV infection affected specific motor and cognitive tasks in conjunction with viral burden and immune responses within the brain. Neonatal animals were infected with a neurovirulent FIV strain (FIV-Ch) and assessed in terms of systemic immune parameters, viral burden, neurobehavioral performance, and neuropathological features. FIV-infected animals displayed less weight gain and lower blood CD4(+) T-cell levels than mock-infected animals (p < 0.05). Gait analyses disclosed greater gait width with increased variation in FIV-infected animals (p < 0.05). Maze performance showed that FIV-infected animals were slower and made more navigational errors than mock-infected animals (p < 0.05). In the object memory test, the FIV-infected group exhibited fewer successful steps with more trajectory errors compared with the mock-infected group (p < 0.05). Performance on the gait, maze, and object memory tests was inversely correlated with F4/80 and CD3 epsilon expression (p < 0.05) and with viral burden in parietal cortex (p < 0.05). Amino acid analysis in cortex showed that D-serine levels were reduced in FIV-infected animals, which was accompanied by diminished kainate and AMPA receptor subunit expression (p < 0.05). The neurobehavioral findings in FIV-infected animals were associated with increased gliosis and reduced cortical neuronal counts (p < 0.05). The present studies indicated that specific motor and neurocognitive abilities were impaired in FIV infection and that these effects were closely coupled with viral burden, neuroinflammation, and neuronal loss.
Maingat
Ferdinand
F
Department of Medicine, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
Vivithanaporn
Pornpun
P
Zhu
Yu
Y
Taylor
Andrew
A
Baker
Glen
G
Pearson
Keir
K
Power
Christopher
C
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology; D015704:CD4 Antigens / Q000378:metabolism; D002415:Cats; D002540:Cerebral Cortex / Q000473:pathology* / Q000821:virology; D002851:Chromatography, High Pressure Liquid; D016181:Feline Acquired Immunodeficiency Syndrome / Q000150:complications / Q000473:pathology / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D007165:Immunosuppression Therapy / Q000662:veterinary; D007794:Lameness, Animal / Q000209:etiology / Q000821:virology; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000821:virology; D020078:Neurogenic Inflammation / Q000209:etiology* / Q000662:veterinary / Q000821:virology; D009474:Neurons / Q000473:pathology* / Q000821:virology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011247:Pregnancy; D013037:Spatial Behavior / Q000502:physiology; D019562:Viral Load / Q000379:methods
D000596:Amino Acids; D015704:CD4 Antigens; D005904:Glial Fibrillary Acidic Protein; D010751:Phosphopyruvate Hydratase