Strain-specific viral distribution and neuropathology of feline immunodeficiency virus

Miller, Craig, Bielefeldt-Ohmann, Helle, Macmillan, Martha, Huitron-Resendiz, Salvador, Henriksen, Steven, Elder, John and Vandewoude, Susan (2011) Strain-specific viral distribution and neuropathology of feline immunodeficiency virus. Veterinary Immunology and Immunopathology, 143 3-4: 282-291. doi:10.1016/j.vetimm.2011.06.006


Author Miller, Craig
Bielefeldt-Ohmann, Helle
Macmillan, Martha
Huitron-Resendiz, Salvador
Henriksen, Steven
Elder, John
Vandewoude, Susan
Title Strain-specific viral distribution and neuropathology of feline immunodeficiency virus
Journal name Veterinary Immunology and Immunopathology   Check publisher's open access policy
ISSN 0165-2427
1873-2534
Publication date 2011-10-15
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.vetimm.2011.06.006
Open Access Status Not yet assessed
Volume 143
Issue 3-4
Start page 282
End page 291
Total pages 10
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Subject 2403 Immunology
3400 Veterinary
Abstract Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of domestic cats, and is the causative agent of feline AIDS. Similar to human immunodeficiency virus (HIV), the pathogenesis of FIV involves infection of lymphocytes and macrophages, and results in chronic progressive immune system collapse and death. Neuropathologic correlates of FIV infection have not yet been elucidated, and may be relevant to understanding HIV-associated neurologic disease (neuroAIDS). As in HIV, FIV strains have been shown to express differential tendencies towards development of clinical neuroAIDS. To interrogate viral genetic determinants that might contribute to neuropathogenicity, cats were exposed to two well-characterized FIV strains with divergent clinical phenotypes and a chimeric strain as follows: FIV (PPR, relatively apathogenic but associated with neurologic manifestations), FIV (C36, immunopathogenic but without associated neurologic disease), and Pcenv (a chimeric virus consisting of a PPR backbone with substituted C36 env region). A sham inoculum control group was also included. Peripheral nerve conduction velocity, CNS imaging studies, viral loads and hematologic analysis were performed over a 12 month period. At termination of the study (350 days post-inoculation), brain sections were obtained from four anatomic locations known to be involved in human and primate lentiviral neuroAIDS. Histological and immunohistochemical evaluation with seven markers of inflammation revealed that Pcenv infection resulted in mild inflammation of the CNS, microglial activation, neuronal degeneration and apoptosis, while C36 and PPR strains induced minimal neuropathologic changes. Conduction velocity aberrations were noted peripherally in all three groups at 63 weeks post-infection. Pcenv viral load in this study was intermediate to the parental strains (C36 demonstrating the highest viral load and PPR the lowest). These results collectively suggest that (i) 3' C36 genomic elements contribute to viral replication characteristics, and (ii) 5' PPR genomic elements contribute to CNS manifestations. This study illustrates the potential for FIV to provide valuable information about neuroAIDS pathogenesis related to genotype and viral kinetics, as well as to identify strains useful to evaluation of therapeutic intervention.
Formatted abstract
Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus of domestic cats, and is the causative agent of feline AIDS. Similar to human immunodeficiency virus (HIV), the pathogenesis of FIV involves infection of lymphocytes and macrophages, and results in chronic progressive immune system collapse and death. Neuropathologic correlates of FIV infection have not yet been elucidated, and may be relevant to understanding HIV-associated neurologic disease (neuroAIDS). As in HIV, FIV strains have been shown to express differential tendencies towards development of clinical neuroAIDS. To interrogate viral genetic determinants that might contribute to neuropathogenicity, cats were exposed to two well-characterized FIV strains with divergent clinical phenotypes and a chimeric strain as follows: FIVPPR (PPR, relatively apathogenic but associated with neurologic manifestations), FIVC36 (C36, immunopathogenic but without associated neurologic disease), and Pcenv (a chimeric virus consisting of a PPR backbone with substituted C36 env region). A sham inoculum control group was also included. Peripheral nerve conduction velocity, CNS imaging studies, viral loads and hematologic analysis were performed over a 12 month period. At termination of the study (350 days post-inoculation), brain sections were obtained from four anatomic locations known to be involved in human and primate lentiviral neuroAIDS. Histological and immunohistochemical evaluation with seven markers of inflammation revealed that Pcenv infection resulted in mild inflammation of the CNS, microglial activation, neuronal degeneration and apoptosis, while C36 and PPR strains induced minimal neuropathologic changes. Conduction velocity aberrations were noted peripherally in all three groups at 63 weeks post-infection. Pcenv viral load in this study was intermediate to the parental strains (C36 demonstrating the highest viral load and PPR the lowest). These results collectively suggest that (i) 3' C36 genomic elements contribute to viral replication characteristics, and (ii) 5' PPR genomic elements contribute to CNS manifestations. This study illustrates the potential for FIV to provide valuable information about neuroAIDS pathogenesis related to genotype and viral kinetics, as well as to identify strains useful to evaluation of therapeutic intervention.
Keyword Lentiviral neuropathology
NeuroAIDS
Feline immunodeficiency virus
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID AI048411
Institutional Status UQ
Additional Notes 10th International Feline Retrovirus Research Symposium 2010

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Veterinary Science Publications
 
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Created: Thu, 13 Oct 2011, 19:49:18 EST by Dr Helle Bielefeldt-ohmann on behalf of School of Veterinary Science