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Published on: September 7, 2017
Neurophysiologic and immunologic abnormalities associated with feline immunodeficiency virus molecular clone FIV-PPR
A J Phipps1, K A Hayes, W R Buck
1Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, USA.
Abstract:
Although direct feline immunodeficiency virus (FIV) proviral DNA inoculation has been shown to be infectious in cats, long-term studies to assess the pathogenic nature of DNA inoculation are lacking. We have recently reported that direct feline leukemia virus (FeLV) DNA inoculation resulted in infection and the development of FeLV-related disease end points with similar temporal expression and virulence to that of cats infected with whole virus. We show in this study that pFIV-PPR DNA inoculation resulted in infection of cats and the development of FIV-related immunologic and neurologic abnormalities. Infected cats demonstrated progressive loss of CD4+ lymphocytes resulting in decreased CD4:CD8 ratios. Neurologic dysfunction was demonstrated by increased bilateral frontal lobe slow-wave activity. Prolongation of the visual evoked potential peak latency onset response pattern also supported a similar progression of abnormal cortical response. Furthermore, histopathologic examination revealed lesions attributed to FIV infection in lymph node, thymus, brain, and lung. Finally, nested polymerase chain reaction detected FIV provirus in brain, bone marrow, mesenteric lymph node, thymus, spleen, tonsil, and liver. These results confirm that FIV DNA inoculation is an efficient model for study of the pathogenic nature of molecular clones in vivo and offers the opportunity to measure temporal genomic stability of a homogeneous challenge material.
Insights
Direct feline immunodeficiency virus (FIV) DNA inoculation effectively infects cats, causing immunologic and neurologic disease similar to whole virus infection. This study validates FIV DNA inoculation as a reliable model for studying viral pathogenesis and genomic stability in vivo.
Area of Science:
- Veterinary Virology
- Immunology
- Neurology
Background:
- Direct feline immunodeficiency virus (FIV) proviral DNA inoculation's long-term pathogenicity in cats remains understudied.
- Previous research demonstrated feline leukemia virus (FeLV) DNA inoculation's efficacy in causing disease similar to whole virus infection.
Purpose of the Study:
- To assess the pathogenic nature of pFIV-PPR DNA inoculation in cats.
- To evaluate FIV-related immunologic and neurologic abnormalities following DNA inoculation.
- To establish FIV DNA inoculation as a model for in vivo molecular clone pathogenesis studies.
Main Methods:
- Inoculation of cats with pFIV-PPR DNA.
- Monitoring of CD4+ lymphocyte counts and CD4:CD8 ratios.
- Assessment of neurologic function via electroencephalography (EEG) and visual evoked potentials (VEPs).
- Histopathologic examination of tissues.
- Nested polymerase chain reaction (PCR) for FIV provirus detection.
Main Results:
- FIV DNA inoculation resulted in infection and development of FIV-related immunologic and neurologic abnormalities.
- Progressive CD4+ lymphocyte loss and decreased CD4:CD8 ratios were observed.
- Increased frontal lobe slow-wave activity and prolonged VEP latency indicated neurologic dysfunction.
- Histopathology revealed FIV-related lesions in multiple organs, including brain, lymph nodes, thymus, and lungs.
- FIV provirus was detected in various tissues, confirming systemic infection.
Conclusions:
- FIV DNA inoculation is an efficient and infectious model for studying feline immunodeficiency virus pathogenesis in vivo.
- This model allows for the assessment of temporal genomic stability of homogeneous challenge materials.
- FIV DNA inoculation effectively mimics the disease progression and virulence of traditional whole virus infections.
