scholarly journals Binding of LFA-1 (CD11a) to Intercellular Adhesion Molecule 3 (ICAM-3; CD50) and ICAM-2 (CD102) Triggers Transmigration of Human Immunodeficiency Virus Type 1-Infected Monocytes through Mucosal Epithelial Cells

2002 ◽  
Vol 76 (1) ◽  
pp. 32-40 ◽  
Author(s):  
Marie-Paule Carreno ◽  
Nicolas Chomont ◽  
Michel D. Kazatchkine ◽  
Theano Irinopoulou ◽  
Corrine Krief ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Epithelial Cells ◽  
Adhesion Molecule ◽  
Mononuclear Cells ◽  
Sexual Transmission ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Transmigration of human immunodeficiency virus (HIV)-infected mononuclear cells through the genital mucosa is one of the possible mechanisms of sexual transmission of HIV. Here, we investigated the transmigration of cell-associated R5-tropic HIV type 1 (HIV-1) through a tight monolayer of human epithelial cells in vitro. We show that this process is dependent on an initial interaction between αLβ2 integrin CD11a/CD18 on infected monocytic cells and intercellular adhesion molecule 2 (ICAM-2; CD102) and ICAM-3 (CD50) on the apical membrane of epithelial cells. The CD50 and CD102 ligands were overexpressed on epithelial cells when the cells were activated by proinflammatory cytokines in the cellular microenvironment. An accumulation of proviral DNA was found in the transmigrated cells, clearly reflecting the preferential transepithelial migration of HIV-1-infected cells under proinflammatory conditions. Our observations provide new insights supporting the hypothesis that HIV-infected mononuclear cells contained in genital secretions from infected individuals may cross the epithelial genital mucosa of an exposed receptive sexual partner, particularly under inflammatory conditions of damaged genital tissue. Understanding the fundamental aspects of the initial HIV entry process during sexual transmission remains a critical step for preventing human infection and developing further vaccinal strategies and virucidal agents.

scholarly journals Statin Compounds Reduce Human Immunodeficiency Virus Type 1 Replication by Preventing the Interaction between Virion-Associated Host Intercellular Adhesion Molecule 1 and Its Natural Cell Surface Ligand LFA-1

2004 ◽  
Vol 78 (21) ◽  
pp. 12062-12065 ◽  
Author(s):  
Jean-François Giguère ◽  
Michel J. Tremblay
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT A variety of host factors, including membrane proteins acquired by human immunodeficiency virus type 1 (HIV-1), play a dominant role in HIV-1 adsorption onto host cells. Examples include the integrin intercellular adhesion molecule 1 (ICAM-1), which, once acquired by HIV-1, promotes virus infectivity via ligation to LFA-1. We tested the ability of statins to diminish HIV-1 replication, based on the idea that these compounds have been shown to block ICAM-1-LFA-1 interactions. Our data indicate that statins diminish HIV-1 attachment to target cells by suppressing ICAM-1-LFA-1 interactions. The capacity of statins to limit the initial steps in virus replication could represent an interesting approach for the treatment of HIV-1 infection.

scholarly journals Enhancement of Human Immunodeficiency Virus Type 1 Replication Is Not Intrinsic to All Polyanion-Based Microbicides

2009 ◽  
Vol 53 (8) ◽  
pp. 3565-3568 ◽  
Author(s):  
Secondo Sonza ◽  
Adam Johnson ◽  
David Tyssen ◽  
Tim Spelman ◽  
Gareth R. Lewis ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Sexual Transmission ◽  
Intrinsic Property ◽  
Enhancement Effect ◽  
Peripheral Blood Mononuclear ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Polyanion-based microbicides have been developed to prevent the sexual transmission of human immunodeficiency virus (HIV). Recent data suggest that polyanions have the capacity to enhance HIV type 1 (HIV-1) replication at threshold antiviral concentrations. Evaluation of the microbicide candidates SPL7013 and PRO 2000 revealed no specific enhancement of two CCR5 HIV-1 strains in human peripheral blood mononuclear cells compared to enfuvirtide (Fuzeon). The enhancement effect is likely to be a function of the assay conditions and is not an intrinsic property of these polyanions.

scholarly journals In Vitro Comparison of Topical Microbicides for Prevention of Human Immunodeficiency Virus Type 1 Transmission

2004 ◽  
Vol 48 (10) ◽  
pp. 3834-3844 ◽  
Author(s):  
Charlene S. Dezzutti ◽  
V. Nicole James ◽  
Artur Ramos ◽  
Sharon T. Sullivan ◽  
Aladin Siddig ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Epithelial Cells ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Immunodeficiency Virus ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT A standardized protocol was used to compare cellular toxicities and anti-human immunodeficiency virus type 1 (HIV-1) activities of candidate microbicides formulated for human use. The microbicides evaluated were cellulose acetate phthalate (CAP), Carraguard, K-Y plus nonoxynol-9 (KY-N9), PRO 2000 (0.5 and 4%), SPL7013 (5%), UC781 (0.1 and 1%), and Vena Gel, along with their accompanying placebos. Products were evaluated for toxicity on cervical and colorectal epithelial cell lines, peripheral blood mononuclear cells (PBMCs), and macrophages (MΦ) by using an ATP release assay, and they were tested for their effect on transepithelial resistance (TER) of polarized epithelial monolayers. Anti-HIV-1 activity was evaluated in assays for transfer of infectious HIV-1 from epithelial cells to activated PBMCs and for PBMC and MΦ infection. CAP, Carraguard, PRO 2000, SPL7013, and UC781 along with their placebos were 20- to 50-fold less toxic than KY-N9 and Vena Gel. None of the nontoxic product concentrations disrupted the TER. Transfer of HIV-1Ba-L from epithelial cells to PBMCs and PBMC and MΦ infection with laboratory-adapted HIV-1Ba-L and HIV-1LAI isolates were inhibited by all products except Carraguard, KY-N9, and Vena Gel. KY-N9, Vena Gel, and Carraguard were not effective in blocking PBMC infection with primary HIV-1A, HIV-1C, and HIV-1CRF01-AE isolates. The concordance of these toxicity results with those previously reported indicates that our protocol may be useful for predicting toxicity in vivo. Moreover, our systematic anti-HIV-1 testing provides a rational basis for making better informed decisions about which products to consider for clinical trials.

scholarly journals Mechanism of Action and In Vitro Activity of 1′,3′-Dioxolanylpurine Nucleoside Analogues against Sensitive and Drug-Resistant Human Immunodeficiency Virus Type 1 Variants

1999 ◽  
Vol 43 (10) ◽  
pp. 2376-2382 ◽  
Author(s):  
Zhengxian Gu ◽  
Mark A. Wainberg ◽  
Nghe Nguyen-Ba ◽  
Lucille L’Heureux ◽  
Jean-Marc de Muys ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mononuclear Cells ◽  
Nucleoside Analogues ◽  
Drug Resistant ◽  
Immunodeficiency Virus ◽  
Blood Mononuclear Cells ◽  
Anti Hiv ◽  
Hiv 1

ABSTRACT (−)-β-d-1′,3′-Dioxolane guanosine (DXG) and 2,6-diaminopurine (DAPD) dioxolanyl nucleoside analogues have been reported to be potent inhibitors of human immunodeficiency virus type 1 (HIV-1). We have recently conducted experiments to more fully characterize their in vitro anti-HIV-1 profiles. Antiviral assays performed in cell culture systems determined that DXG had 50% effective concentrations of 0.046 and 0.085 μM when evaluated against HIV-1IIIB in cord blood mononuclear cells and MT-2 cells, respectively. These values indicate that DXG is approximately equipotent to 2′,3′-dideoxy-3′-thiacytidine (3TC) but 5- to 10-fold less potent than 3′-azido-2′,3′-dideoxythymidine (AZT) in the two cell systems tested. At the same time, DAPD was approximately 5- to 20-fold less active than DXG in the anti-HIV-1 assays. When recombinant or clinical variants of HIV-1 were used to assess the efficacy of the purine nucleoside analogues against drug-resistant HIV-1, it was observed that AZT-resistant virus remained sensitive to DXG and DAPD. Virus harboring a mutation(s) which conferred decreased sensitivity to 3TC, 2′,3′-dideoxyinosine, and 2′,3′-dideoxycytidine, such as a 65R, 74V, or 184V mutation in the viral reverse transcriptase (RT), exhibited a two- to fivefold-decreased susceptibility to DXG or DAPD. When nonnucleoside RT inhibitor-resistant and protease inhibitor-resistant viruses were tested, no change in virus sensitivity to DXG or DAPD was observed. In vitro drug combination assays indicated that DXG had synergistic antiviral effects when used in combination with AZT, 3TC, or nevirapine. In cellular toxicity analyses, DXG and DAPD had 50% cytotoxic concentrations of greater than 500 μM when tested in peripheral blood mononuclear cells and a variety of human tumor and normal cell lines. The triphosphate form of DXG competed with the natural nucleotide substrates and acted as a chain terminator of the nascent DNA. These data suggest that DXG triphosphate may be the active intracellular metabolite, consistent with the mechanism by which other nucleoside analogues inhibit HIV-1 replication. Our results suggest that the use of DXG and DAPD as therapeutic agents for HIV-1 infection should be explored.

scholarly journals Grossly Defective nef Gene Sequences in a Human Immunodeficiency Virus Type 1-Seropositive Long-Term Nonprogressor

1998 ◽  
Vol 72 (5) ◽  
pp. 3646-3657 ◽  
Author(s):  
Roberto Salvi ◽  
Anna Rosa Garbuglia ◽  
Antonino Di Caro ◽  
Simonetta Pulciani ◽  
Francesco Montella ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Length Polymorphism ◽  
Mononuclear Cells ◽  
Polymorphism Analysis ◽  
Immunodeficiency Virus ◽  
Peripheral Mononuclear Cells ◽  
Hiv 1

ABSTRACT We have been investigating a long-term nonprogressor who was found to be human immunodeficiency virus type 1 (HIV-1) seropositive in 1985 and has survived with stable CD4+ T-cell counts (>1,000 CD4 cells/μl) without any AIDS-related illness. We have previously reported that repeated attempts to measure HIV-1 RNA in the peripheral mononuclear cells obtained from this subject have invariably failed. In the present study, we have analyzed the molecular nature of the HIV-1 quasispecies infecting this patient by PCR amplification of two proviral regions, the 5′ long terminal repeat (5′LTR)/gagleader and the nef gene, directly from fresh uncultured peripheral mononuclear cells, followed by length polymorphism analysis (with 1994, 1995, and 1996 samples) and sequencing (with a 1996 sample). Only proviral forms with nef deletions were revealed by length polymorphism analysis in samples from all three time points. Sequence analysis of the nef gene from the 1996 sample confirmed the presence of similar proviral quasispecies characterized by the presence of several deletions located in thenef-alone and the nef/U3 overlapping regions. Length polymorphism analysis of the 5′LTR/gag leader region suggested the existence of two major quasispecies populations, one characterized by the presence of forms carrying deletions in the U3 region and the other showing a completely intact, full-length 5′LTR. Evidence of the role of nef gene defects in long-term survival of HIV-1-infected patients has been provided so far in two independent investigations involving patients infected with HIV through blood transfusion. Here we show the existence of a similar condition in a subject who acquired HIV-1 seropositivity through the sexual route.

scholarly journals Human immunodeficiency virus types 1 and 2 have different replication kinetics in human primary macrophage culture

2006 ◽  
Vol 87 (2) ◽  
pp. 411-418 ◽  
Author(s):  
David Marchant ◽  
Stuart J. D. Neil ◽  
Áine McKnight
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Steady Rate ◽  
Immunodeficiency Virus ◽  
Load Characteristics ◽  
Kinetics Of ◽  
Hiv 1

This study compares the replication of primary isolates of human immunodeficiency virus type 2 (HIV-2) and type 1 (HIV-1) in monocyte-derived macrophages (MDMs). Eleven HIV-2 and five HIV-1 primary isolates that use CCR5, CXCR4 or both coreceptors to enter cells were included. Regardless of coreceptor preference, 10 of 11 HIV-2 viruses could enter, reverse transcribe and produce fully infectious virus in MDMs with efficiency equal to that in peripheral blood mononuclear cells. However, the kinetics of replication of HIV-2 compared with HIV-1 over time were distinct. HIV-2 had a burst of virus replication 2 days after infection that resolved into an apparent ‘latent state’ at day 3. HIV-1, however, continued to produce infectious virions at a lower, but steady, rate throughout the course of infection. These results may have implications for the lower pathogenesis and viral-load characteristics of HIV-2 infection.

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