title: Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus.
abstract: Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs.
authors.affiliation: Department of Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America.
authors.forename: C D
authors.identifier: http://orcid.org/0000-0002-6844-0251
authors.initials: CD
authors.lastname: Eckstrand
authors.affiliation: Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
authors.forename: E E
authors.initials: EE
authors.lastname: Sparger
authors.affiliation: Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
authors.forename: K A
authors.initials: KA
authors.lastname: Pitt
authors.affiliation: Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California Davis, Davis, California, United States of America.
authors.forename: B G
authors.initials: BG
authors.lastname: Murphy
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002415:Cats; D002908:Chronic Disease; D018450:Disease Progression; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology*; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000502:physiology; D008212:Lymphocyte Depletion; D008221:Lymphoid Tissue / Q000276:immunology / Q000821:virology; D014779:Virus Replication