Neurologic dysfunctions caused by a molecular clone of feline immunodeficiency virus, FIV-PPR.
FIV is a lentivirus of domestic cats that causes a spectrum of diseases that is remarkably similar to the clinical syndrome produced by HIV infection in people. Both HIV and FIV has been shown to cause neurologic dysfunction. Specific Pathogen-Free (SPF) cats were placed into one of three groups: FIV-PPR infected; DU-FIV-PPR (a dUTPase mutant of the FIV-PPR clone) infected; or an age-matched control group. In both infected groups, the general clinical signs of infection included lymphadenopathy, oral ulcerations, rough hair coat, and conjuntivitis. Specific neurological changes in the FIV-PPR infected cats included hind limb paresis; delayed righting and pupillary reflexes; behavioral changes; delayed visual and auditory evoked potentials; decreased spinal and peripheral nerve conduction velocities; and marked alterations in sleep patterns. Most of these changes were also observed in the DU-FIV-PPR infected cats. However, these cats tended to have a slightly less severe disease. In this study, we have demonstrated that an infectious molecular clone of FIV closely parallels the disease course of wild type FIV-infected cats. By using a knockout gene mutant of this clone, we were able to demonstrate that the dUTPase gene is not essential for neuropathogenesis. Further use of the FIV-PPR clone should prove useful in determining the essential viral elements that are important in the neuropathogenesis of lentiviral infections.
Phillips
T R
TR
Neuropharmacology, Scripps Research Institute, La Jolla California 92037, USA.
Prospero-Garcia
O
O
Wheeler
D W
DW
Wagaman
P C
PC
Lerner
D L
DL
Fox
H S
HS
Whalen
L R
LR
Bloom
F E
FE
Elder
J H
JH
Henriksen
S J
SJ
D000818:Animals; D002415:Cats; D003001:Cloning, Molecular; D004569:Electroencephalography; D016057:Evoked Potentials, Auditory, Brain Stem; D005073:Evoked Potentials, Somatosensory; D016181:Feline Acquired Immunodeficiency Syndrome / Q000503:physiopathology* / Q000821:virology; D005814:Genes, Viral / Q000235:genetics; D016089:Immunodeficiency Virus, Feline / Q000235:genetics* / Q000472:pathogenicity; D016296:Mutagenesis / Q000502:physiology; D009422:Nervous System Diseases / Q000503:physiopathology / Q000821:virology*; D009431:Neural Conduction / Q000502:physiology; D010525:Peripheral Nerves / Q000201:enzymology / Q000503:physiopathology / Q000821:virology; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism; D012890:Sleep / Q000502:physiology; D013116:Spinal Cord / Q000201:enzymology / Q000503:physiopathology / Q000821:virology; D014774:Virulence
D011755:Pyrophosphatases; C023278:uridine triphosphatase