Engagement of CD43 Enhances Human Immunodeficiency Virus Type 1 Transcriptional Activity and Virus Production That Is Induced upon TCR/CD3 Stimulation

Abstract

Human immunodeficiency virus type 1 (HIV-1) transcriptional activity is regulated by several cytokines and T cell activators. CD43 (sialophorin) is a sialoglycoprotein expressed on the surface of a wide variety of blood cells including T lymphocytes. Several studies have shown that CD43 ligation induces proliferation and activation of human T lymphocytes. We were thus interested in defining whether CD43-mediated signaling events can modulate the life cycle of HIV-1. We demonstrate here that CD43 cross-linking potentiates HIV-1 promoter-driven activity and virus production that is seen following the engagement of the T-cell receptor (TCR)⅐CD3 complex. This effect is independent of the CD28 co-stimulatory molecule and is mediated by both NF-B and NFAT transcription factors. A number of signal transducers known to be involved in the TCR/CD3-dependent signal transduction pathway, including p56 lck , p36 lat , and SLP-76, as well as capacitative entry of calcium, are crucial for the noticed CD43 co-stimulatory effect. Calcium mobilization studies indicate that a synergy is occurring between CD43-and TCR/CD3-mediated signaling events leading to an augmented calcium release. These data suggest that CD43 can be seen as a co-stimulatory cell surface constituent that can modulate HIV-1 expression in T lymphocytes.

Engagement of ICAM-3 Provides a Costimulatory Signal for Human Immunodeficiency Virus Type 1 Replication in both Activated and Quiescent CD4+T Lymphocytes: Implications for Virus Pathogenesis

“…2A). It has already been reported that this signal can be the result of overlapping NF-B and NFAT complexes (3,4). The binding of NF-B was confirmed by supershift with anti-NF-B p50 antibodies ( Fig.…”

“…An increasing number of accessory cell surface molecules are also involved in upregulation of T-cell activation (reviewed in reference 51). For example, we have recently demonstrated that CD43 functions as a potent costimulatory molecule for TCR/CD3-dependent induction of HIV-1 LTR-driven transcription and virus production (3). Another molecule of great interest in that respect is the intercellular adhesion molecule 3 (ICAM-3, or CD50), a 120-kDa, highly expressed cell surface antigen restricted to the leukocyte cell lineage (1,20,24).…”

The CD43 Coreceptor Molecule Recruits the ζ-Chain as Part of Its Signaling Pathway

“…Recently, CD43-dependent signals were shown to enhance HIV type 1 transcriptional activity and virus production induced through TCR stimulation (48). Interestingly, Lck, and the scaffold proteins LAT and SLP-76 were all required for the HIV-1 transcriptional activity mediated through TCR and CD43 costimulation, suggesting a crucial role for Lck, LAT, and SLP-76 in the CD43-mediated signaling pathway.…”

TLR2 Signaling Renders Quiescent Naive and Memory CD4+ T Cells More Susceptible to Productive Infection with X4 and R5 HIV-Type 1

“…As a positive control, we used CD4 ϩ T cells (5 ϫ 10 6 ) that were activated for 3 days with PHA-L (1 g/ml) in the presence of rhIL-2 (30 U/ml) and stimulated for 4 h with OKT3 (1 g/ml) and anti-CD28 (1 g/ml) in a final volume of 2.5 ml of RPMI 1640. Cells were then washed twice with ice-cold PBS, and nuclear extracts were prepared according to a previously reported protocol (37). EMSAs were performed by incubating 10 g of nuclear proteins with 20 l of 1ϫ binding buffer (10 mM HEPES (pH 7.9), 4% glycerol, 1% Ficoll, 25 mM KCl, 1 mM DTT, 0.5 mM EDTA, 25 mM NaCl) containing 2 g of poly(dI-dC), 10 g of nuclease-free BSA fraction V, and 0.8 ng of a [␥-32 P]dsDNA oligonucleotide for 20 min at room temperature.…”