CD8+ T cells from feline immunodeficiency virus (FIV) infected cats suppress exogenous FIV replication of their peripheral blood mononuclear cells in vitro

2002 ◽  
Vol 147 (8) ◽  
pp. 1517-1529 ◽  
Author(s):  
T. Hohdatsu ◽  
T. Sasagawa ◽  
A. Yamazaki ◽  
K. Motokawa ◽  
H. Kusuhara ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Cd8 T Cells ◽  
Feline Immunodeficiency Virus ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Immunodeficiency Virus ◽  
Blood Mononuclear Cells

scholarly journals In Vivo Antiretroviral Activity of Stampidine in Chronically Feline Immunodeficiency Virus-Infected Cats

2003 ◽  
Vol 47 (4) ◽  
pp. 1233-1240 ◽  
Author(s):  
Fatih M. Uckun ◽  
Chun-Lin Chen ◽  
Peter Samuel ◽  
Sharon Pendergrass ◽  
T. K. Venkatachalam ◽  
...  
Keyword(s):  
Dose Level ◽  
Peripheral Blood Mononuclear Cells ◽  
Feline Immunodeficiency Virus ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Immunodeficiency Virus ◽  
Blood Mononuclear Cells ◽  
Antiretroviral Activity

ABSTRACT Here we report the antiretroviral activity of the experimental nucleoside reverse transcriptase inhibitor (NRTI) compound stampidine in cats chronically infected with feline immunodeficiency virus (FIV). Notably, a single oral bolus dose of 50 or 100 mg of stampidine per kg resulted in a transient ≥1-log decrease in the FIV load of circulating peripheral blood mononuclear cells in five of six FIV-infected cats and no side effects. A 4-week stampidine treatment course with twice-daily administration of hard gelatin capsules containing 25 to 100 mg of stampidine per kg was also very well tolerated by cats at cumulative dose levels as high as 8.4 g/kg and exhibited a dose-dependent antiretroviral effect. One of three cats treated at the 25-mg/kg dose level, three of three cats treated at the 50-mg/kg dose level, and three of three cats treated at the 100-mg/kg dose level (but none of three control cats treated with placebo pills) showed a therapeutic response, as evidenced by a ≥1-log reduction in the FIV load in peripheral blood mononuclear cells within 2 weeks. The previously documented in vitro and in vivo antiretroviral activity of stampidine against primary clinical human immunodeficiency virus type 1 isolates with genotypic and/or phenotypic NRTI resistance, together with its favorable animal toxicity profile, pharmacokinetics, and in vivo antiretroviral activity in FIV-infected cats, warrants further development of this promising new NRTI compound.

scholarly journals Quantification of Feline immunodeficiency virus (FIVpco) in peripheral blood mononuclear cells, lymph nodes and plasma of naturally infected cougars

2006 ◽  
Vol 87 (4) ◽  
pp. 967-975 ◽  
Author(s):  
David J. Blake ◽  
Jon Graham ◽  
Mary Poss
Keyword(s):  
Virus Replication ◽  
Peripheral Blood Mononuclear Cells ◽  
Feline Immunodeficiency Virus ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Domestic Cats ◽  
Peripheral Blood Mononuclear ◽  
Viral Loads ◽  
Immunodeficiency Virus ◽  
Blood Mononuclear Cells

Infection of domestic cats with Feline immunodeficiency virus (FIV) results in a fatal immunodeficiency disease, similar to Human immunodeficiency virus 1 (HIV-1) in humans. Elevated plasma viral loads in domestic cats are correlated to decreased survival time and disease progression. However, FIV is also maintained as an apathogenic infection in other members of the family Felidae including cougars, Puma concolor (FIVpco). It is not known whether the lack of disease in cougars is a result of diminished virus replication. A real-time PCR assay was developed to quantify both FIVpco proviral and plasma viral loads in naturally infected cougars. Proviral loads quantified from peripheral blood mononuclear cells (PBMC) ranged from 2·90×101 to 6·72×104 copies per 106 cells. Plasma viral loads ranged from 2·30×103 to 2·81×106 RNA copies ml−1. These data indicate that FIVpco viral loads are comparable to viral loads observed in endemic and epidemic lentivirus infections. Thus, the lack of disease in cougars is not due to low levels of virus replication. Moreover, significant differences observed among cougar PBMC proviral loads correlated to viral lineage and cougar age (P=0·014), which suggests that separate life strategies exist within FIVpco lineages. This is the first study to demonstrate that an interaction of lentivirus lineage and host age significantly effect proviral loads.

scholarly journals Human Immunodeficiency Virus Type 1 DNA Sequences Genetically Damaged by Hypermutation Are Often Abundant in Patient Peripheral Blood Mononuclear Cells and May Be Generated during Near-Simultaneous Infection and Activation of CD4+ T Cells

2001 ◽  
Vol 75 (17) ◽  
pp. 7973-7986 ◽  
Author(s):  
Mario Janini ◽  
Melissa Rogers ◽  
Deborah R. Birx ◽  
Francine E. McCutchan
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Immunodeficiency Virus ◽  
Blood Mononuclear Cells ◽  
Hiv 1

ABSTRACT G-to-A hypermutation has been sporadically observed in human immunodeficiency virus type 1 (HIV-1) proviral sequences from patient peripheral blood mononuclear cells (PBMC) and virus cultures but has not been systematically evaluated. PCR primers matched to normal and hypermutated sequences were used in conjunction with an agarose gel electrophoresis system incorporating an AT-binding dye to visualize, separate, clone, and sequence hypermutated and normal sequences in the 297-bp HIV-1 protease gene amplified from patient PBMC. Among 53 patients, including individuals infected with subtypes A through D and at different clinical stages, at least 43% of patients harbored abundant hypermutated, along with normal, protease genes. In 70 hypermutated sequences, saturation of G residues in the GA or GG dinucleotide context ranged from 20 to 94%. Levels of other mutants were not elevated, and G-to-A replacement was entirely restricted to GA or GG, and not GC or GT, dinucleotides. Sixty-nine of 70 hypermutated and 3 of 149 normal sequences had in-frame stop codons. To investigate the conditions under which hypermutation occurs in cell cultures, purified CD4+ T cells from normal donors were infected with cloned NL4-3 virus stocks at various times before and after phytohemagglutinin (PHA) activation. Hypermutation was pronounced when HIV-1 infection occurred simultaneously with, or a few hours after, PHA activation, but after 12 h or more after PHA activation, most HIV-1 sequences were normal. Hypermutated sequences generated in culture corresponded exactly in all parameters to those obtained from patient PBMC. Near-simultaneous activation and infection of CD4+ T cells may represent a window of susceptibility where the informational content of HIV-1 sequences is lost due to hypermutation.

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