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Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Peripheral blood leukocyte subset frequencies six years post infection.FIV-infected progressor cats show a markedly lower frequency of CD4+ T cells in the peripheral blood compared to uninfected cats. FIV-infected cats (including the LTNP cat) also show a greater frequency of CD11b+ cells. A notable difference in CD8+, and CD21+ and CD11b+ leukocyte subsets was not detected; however statistics were not performed due to low cat numbers. Boxes represent the mean and whiskers represent the numeric range.
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pone.0175327.g001: Peripheral blood leukocyte subset frequencies six years post infection.FIV-infected progressor cats show a markedly lower frequency of CD4+ T cells in the peripheral blood compared to uninfected cats. FIV-infected cats (including the LTNP cat) also show a greater frequency of CD11b+ cells. A notable difference in CD8+, and CD21+ and CD11b+ leukocyte subsets was not detected; however statistics were not performed due to low cat numbers. Boxes represent the mean and whiskers represent the numeric range.

Mentions: Frequencies and absolute number of peripheral blood CD4+ and CD8+ leukocytes, CD21+ B cells, and CD11b+ leukocytes were determined for FIV-infected progressor and long-term non-progressor cats by flow cytometry and compared to uninfected cats (Fig 1). The mean frequency and absolute number of circulating CD4+ T-cells of FIV-infected progressor cats (2.0% and 185 cells/μl ± 93.7, respectively) were greatly reduced relative to uninfected cats at the time of surgery (17.1% and 3770 cells/μl ± 354). The FIV-infected LTNP cat demonstrated a peripheral blood CD4+ leukocyte frequency and absolute count essentially indistinguishable from those of the uninfected cats (13.7% and 3700 cells/μl). Severe peripheral blood CD4+ depletion, as observed for the FIV-infected progressor cats, is a hallmark of FIV infection in cats.[9,11] Due to low animal numbers, statistical comparisons could not be performed. Subjectively, differences in the frequencies of CD8+ and CD21+ leukocytes were not observed in the peripheral blood; however all FIV-infected cats (including the LTNP cat) showed a higher frequency of peripheral CD11b+ cells, which is part of a heterodimeric leukocyte adhesion protein present on feline monocytes, dendritic cells, and neutrophils.[15,16]


Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus
Peripheral blood leukocyte subset frequencies six years post infection.FIV-infected progressor cats show a markedly lower frequency of CD4+ T cells in the peripheral blood compared to uninfected cats. FIV-infected cats (including the LTNP cat) also show a greater frequency of CD11b+ cells. A notable difference in CD8+, and CD21+ and CD11b+ leukocyte subsets was not detected; however statistics were not performed due to low cat numbers. Boxes represent the mean and whiskers represent the numeric range.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5383277&req=5

pone.0175327.g001: Peripheral blood leukocyte subset frequencies six years post infection.FIV-infected progressor cats show a markedly lower frequency of CD4+ T cells in the peripheral blood compared to uninfected cats. FIV-infected cats (including the LTNP cat) also show a greater frequency of CD11b+ cells. A notable difference in CD8+, and CD21+ and CD11b+ leukocyte subsets was not detected; however statistics were not performed due to low cat numbers. Boxes represent the mean and whiskers represent the numeric range.
Mentions: Frequencies and absolute number of peripheral blood CD4+ and CD8+ leukocytes, CD21+ B cells, and CD11b+ leukocytes were determined for FIV-infected progressor and long-term non-progressor cats by flow cytometry and compared to uninfected cats (Fig 1). The mean frequency and absolute number of circulating CD4+ T-cells of FIV-infected progressor cats (2.0% and 185 cells/μl ± 93.7, respectively) were greatly reduced relative to uninfected cats at the time of surgery (17.1% and 3770 cells/μl ± 354). The FIV-infected LTNP cat demonstrated a peripheral blood CD4+ leukocyte frequency and absolute count essentially indistinguishable from those of the uninfected cats (13.7% and 3700 cells/μl). Severe peripheral blood CD4+ depletion, as observed for the FIV-infected progressor cats, is a hallmark of FIV infection in cats.[9,11] Due to low animal numbers, statistical comparisons could not be performed. Subjectively, differences in the frequencies of CD8+ and CD21+ leukocytes were not observed in the peripheral blood; however all FIV-infected cats (including the LTNP cat) showed a higher frequency of peripheral CD11b+ cells, which is part of a heterodimeric leukocyte adhesion protein present on feline monocytes, dendritic cells, and neutrophils.[15,16]

View Article: PubMed Central - PubMed

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.

No MeSH data available.