title: Strain-specific viral distribution and neuropathology of feline immunodeficiency virus.
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) (PPR, relatively apathogenic but associated with neurologic manifestations), FIV(C36) (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.
authors.affiliation: Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1619, USA. craig.miller@colostate.edu
authors.forename: Craig
authors.initials: C
authors.lastname: Miller
authors.forename: Helle
authors.initials: H
authors.lastname: Bielefeldt-Ohmann
authors.forename: Martha
authors.initials: M
authors.lastname: MacMillan
authors.forename: Salvador
authors.initials: S
authors.lastname: Huitron-Resendiz
authors.forename: Steven
authors.initials: S
authors.lastname: Henriksen
authors.forename: John
authors.initials: J
authors.lastname: Elder
authors.forename: Susan
authors.initials: S
authors.lastname: VandeWoude
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D001933:Brain Stem / Q000503:physiopathology / Q000821:virology; D002415:Cats / Q000821:virology; D002490:Central Nervous System / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D016181:Feline Acquired Immunodeficiency Syndrome / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D015683:Gene Products, gag / Q000378:metabolism; D016089:Immunodeficiency Virus, Feline / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000662:veterinary; D012367:RNA, Viral / Q000378:metabolism; D019562:Viral Load / Q000662:veterinary
chemical_list: D015683:Gene Products, gag; D012367:RNA, Viral