scholarly journals Alpha-Cyclodextrin Sulphate, an anti-HIV Agent, Retains its Antiviral Effect in the Presence of Hydrocortisol Phosphate

1993 ◽  
Vol 4 (1) ◽  
pp. 65-66 ◽  
Author(s):  
J. Pitha ◽  
R. Anand
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Antiviral Effect ◽  
Simultaneous Treatment ◽  
Peripheral Blood Mononuclear ◽  
Antiviral Compound ◽  
Cytopathic Effects ◽  
The Stability ◽  
Hiv 1

Cyclodextrin sulphates alpha (a) and beta (b) were found to be inhibitors of replication of human immunodeficiency virus (HIV-1) in phytohaemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC); the same cells were also stimulated to proliferate (Anand et al., 1990). B-Cyclodextrin sulphate was also found to stimulate another, more complex, cell proliferation-neovascularization process in rabbit cornea (Folkman et al., 1989). Since the process of neovascularization is generally associated with progression of tumour growth and other pathologies, it is obvious that its stimulation by an antiviral compound may be a serious side effect. Nevertheless endotoxin-induced neovascularization can be suppressed by simultaneous treatment with b-cyclodextrin sulphate and glucocorticoids (Folkman et al., 1989). The same co-treatment may possibly be used to improve antiviral action of cyclodextrin sulphates, but such a combination therapy may not be free of complications. Glucocorticoids also affect the stability of various cellular membranes. Treatment of cells in vitro by glucocorticoids is known to stabilize their lysozymes. Glucocorticoids affect both the proliferative capacity of the cells (Cristofalo, 1972) and cytopathic effects of rabies viral infection. Furthermore, it has been reported that the cytopathic effects of rabies and of yellow fever viruses were inhibited while those of the polio virus were only mildly affected (Hannoun et al., 1965). Consequently, in this work we evaluated effects of a glucocorticoid and of glucocorticoid-a-cyclodextrin sulphate combination on HIV-1 replication.

scholarly journals In Vitro Interactions between Apricitabine and Other Deoxycytidine Analogues

2007 ◽  
Vol 51 (8) ◽  
pp. 2948-2953 ◽  
Author(s):  
R. Bethell ◽  
J. De Muys ◽  
J. Lippens ◽  
A. Richard ◽  
B. Hamelin ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
High Performance ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Transcriptase Inhibitor ◽  
Reverse Transcriptase Activity ◽  
Peripheral Blood Mononuclear ◽  
Reverse Transcriptase Inhibitor ◽  
Hiv 1

ABSTRACT Apricitabine is a novel deoxycytidine analogue reverse transcriptase inhibitor that is under development for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Apricitabine is phosphorylated to its active triphosphate by deoxycytidine kinase, which is also responsible for the intracellular phosphorylation of lamivudine (3TC) and emtricitabine (FTC); hence, in vitro studies were performed to investigate possible interactions between apricitabine and these agents. Human peripheral blood mononuclear cells (PBMC) were incubated for 24 h with various concentrations of 3H-labeled or unlabeled apricitabine, 3TC, or FTC. Intracellular concentrations of parent compounds and their phosphorylated derivatives were measured by high-performance liquid chromatography. In other experiments, viral reverse transcriptase activity was measured in PBMC infected with HIV-1 bearing M184V in the presence of various concentrations of apricitabine and 3TC. [3H]apricitabine and [3H]3TC were metabolized intracellularly to form mono-, di-, and triphosphates. 3TC and FTC (1 to 10 μM) produced concentration-dependent decreases in apricitabine phosphorylation; in contrast, apricitabine at concentrations of up to 30 μM had no effect on the phosphorylation of 3TC or FTC. The combination of apricitabine and 3TC reduced the antiviral activity of apricitabine against HIV-1: apricitabine concentrations producing 50% inhibition of viral reverse transcriptase were increased two- to fivefold in the presence of 3TC. These findings suggest that nucleoside reverse transcriptase inhibitors with similar modes of action may show biochemical interactions that affect their antiviral efficacy. It is therefore essential that potential interactions between combinations of new and existing agents be thoroughly investigated before such combinations are introduced into clinical practice.

Expression of CD4 on human peripheral blood neutrophils

Blood ◽  
2003 ◽  
Vol 101 (11) ◽  
pp. 4452-4456 ◽  
Author(s):  
Priscilla Biswas ◽  
Barbara Mantelli ◽  
Antonio Sica ◽  
Mauro Malnati ◽  
Carla Panzeri ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Human Herpesvirus ◽  
Peripheral Blood Mononuclear ◽  
Similar Frequency ◽  
Blood Neutrophils ◽  
Hiv 1

Abstract CD4, the primary receptor for entry of HIV, is known to be expressed on T cells and monocytes/macrophages; healthy natural killer (NK) lymphocytes; in vitro human herpesvirus 6 (HHV6)–infected CD8+, NK, and γδ T lymphocytes; CD34+ progenitor cells; and a subset of eosinophils and basophils. We here report the unconventional expression of CD4 at the surface of peripheral blood neutrophils derived from 4 of 51 (7.8%) HIV-1–infected and 3 of 25 (12%) uninfected donors, with similar frequency within the 2 groups. The percentage of CD4+ neutrophils ranged from 39% to 97% of the total neutrophil population. Both surface and cytoplasmic forms of CD4 were present in neutrophils. Quantitative RNA polymerase chain reaction (PCR) revealed that neutrophils contain levels of CD4 mRNA comparable to those of peripheral blood mononuclear cells derived from the same donor. The conformation of CD4 expressed at the surface of neutrophils was similar to that of CD4 expressed on T lymphocytes as determined by the binding of monoclonal antibodies specific for conformational epitopes and the binding of recombinant HIV-1 gp120. Thus, our data provide evidence that neutrophils express endogenous CD4 and bind HIV. Owing to their abundance in peripheral blood, CD4+ neutrophils may influence significantly the biodistribution of HIV delivering it to sites of inflammation or to additional tissue reservoirs.

scholarly journals Identification of HIV-1 Epitopes that Induce the Synthesis of a R5 HIV-1 Suppression Factor by Human CD4+T Cells Isolated from HIV-1 Immunized Hu-PBL SCID Mice

2005 ◽  
Vol 12 (4) ◽  
pp. 235-242 ◽  
Author(s):  
Atsushi Yoshida ◽  
Reiko Tanaka ◽  
Akira Kodama ◽  
Naoki Yamamoto ◽  
Aftab A. Ansari ◽  
...  
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Severe Combined Immunodeficiency ◽  
Scid Mice ◽  
Human Interferon ◽  
Suppression Factor ◽  
Peripheral Blood Mononuclear ◽  
Hiv 1

We have previously reported that immunization of the severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood mononuclear cells (PBMC) (hu-PBL-SCID mice) with inactivated human immunodeficiency virus type-1 (HIV-1)-pulsed-autologous dendritic cells (HIV-DC) elicits HIV-1-reactive CD4+T cells that produce an as yet to be defined novel soluble factorin vitrowith anti-viral properties against CCR5 tropic (R5) HIV-1 infection. These findings led us to perform studies designed to identify the lineage of the cell that synthesizes such a factorin vitroand define the epitopes of HIV-1 protein that have specificity for the induction of such anti-viral factor. Results of our studies show that this property is a function of CD4+but not CD8+T cells. Human CD4+T cells were thus recovered from the HIV-DC-immunized hu-PBL-SCID mice and were re-stimulatedin vitroby co-culture for 2 days with autologous adherent PBMC as antigen presenting cells, APC previously pulsed with inactivated HIV in IL-2-containing medium to expand HIV-1-reactive CD4+T cells. Aliquots of these re-stimulated CD4+T cells were then co-cultured with similar APC's that were previously pulsed with 10 μg/ml of a panel of HIV peptides for an additional 2 days, and their culture supernatants were examined for the production of both the R5 HIV-1 suppression factor and IFN-Υ. The data presented herein show that the HIV-1 primed CD4+T cells produced the R5 suppression factor in response to a wide variety of HIV-1 gag, env, pol, nef or vif peptides, depending on the donor of the CD4+T cells. Simultaneous production of human interferon (IFN)-Υ was observed in some cases. These results indicate that human CD4+T cells in PBMC of HIV-1 naive donors have a wide variety of HIV-1 epitope-specific CD4+T cell precursors that are capable of producing the R5 HIV-1 suppression factor upon DC-based vaccination with whole inactivated HIV-1.

scholarly journals Primary HIV-1 and Infectious Molecular Clones Are Differentially Susceptible to Broadly Neutralizing Antibodies

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 782
Author(s):  
Jiae Kim ◽  
Venigalla B. Rao ◽  
Mangala Rao
Keyword(s):  
Neutralizing Antibodies ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Virus Transmission ◽  
Early Time ◽  
Design Strategies ◽  
Peripheral Blood Mononuclear ◽  
Infectious Molecular Clones ◽  
Hiv 1

To prevent the spread of HIV-1, a vaccine should elicit antibodies that block viral entry for all cell types. Recently, we have developed a virus capture assay to quantitatively examine early time points of infection. Here we present data on the ability of bNAbs to inhibit capture (1 h) or replication (48 h) of purified primary acute or chronic HIV or infectious molecular clones (IMCs) in human peripheral blood mononuclear cells (PBMCs) as quantified by qRT-PCR. Although bNAbs significantly inhibited HIV-1 replication in PBMCs in a virus subtype and in a PBMC-donor specific manner, they did not inhibit virus capture of primary viruses. In contrast, IMC capture and replication in PBMCs and purified CD4+ T cells were significantly inhibited by bNAbs, thus indicating that unlike IMCs, primary HIV-1 may initially bind to other cell surface molecules, which leads to virus capture even in the presence of bNAbs. Our results demonstrate that the initial interactions and some aspects of infectivity of primary HIV-1 and IMCs are inherently different, which underscores the importance of studying virus transmission using primary viruses in in vitro studies, an issue that could impact HIV-1 vaccine design strategies.

scholarly journals Monocyte tissue factor induction by lipopolysaccharide (LPS): dependence on LPS-binding protein and CD14, and inhibition by a recombinant fragment of bactericidal/permeability-increasing protein

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2516-2525 ◽  
Author(s):  
K Meszaros ◽  
S Aberle ◽  
R Dedrick ◽  
R Machovich ◽  
A Horwitz ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Binding Protein ◽  
Mononuclear Phagocytes ◽  
Factor Vii ◽  
Peripheral Blood Mononuclear ◽  
Recombinant Fragment

Abstract Mononuclear phagocytes, stimulated by bacterial lipopolysaccharide (LPS), have been implicated in the activation of coagulation in sepsis and endotoxemia. In monocytes LPS induces the synthesis of tissue factor (TF) which, assembled with factor VII, initiates the blood coagulation cascades. In this study we investigated the mechanism of LPS recognition by monocytes, and the consequent expression of TF mRNA and TF activity. We also studied the inhibition of these effects of LPS by rBPI23, a 23-kD recombinant fragment of bactericidal/permeability increasing protein, which has been shown to antagonize LPS in vitro and in vivo. Human peripheral blood mononuclear cells, or monocytes isolated by adherence, were stimulated with Escherichia coli O113 LPS at physiologically relevant concentrations (> or = 10 pg/mL). The effect of LPS was dependent on the presence of the serum protein LBP (lipopolysaccharide-binding protein), as shown by the potentiating effect of human recombinant LBP or serum. Furthermore, recognition of low amounts of LPS by monocytes was also dependent on CD14 receptors, because monoclonal antibodies against CD14 greatly reduced the LPS sensitivity of monocytes in the presence of serum or rLBP. Induction of TF activity and mRNA expression by LPS were inhibited by rBPI23. The expression of tumor necrosis factor showed qualitatively similar changes. Considering the involvement of LPS-induced TF in the potentially lethal intravascular coagulation in sepsis, inhibition of TF induction by rBPI23 may be of therapeutic benefit.

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