Association of p56lck with the cytoplasmic domain of CD4 modulates HIV-1 expression.

Tremblay, Michel J.; Meloche, Sylvain; Gratton, Sophie; Wainberg, M A; Sékaly, Rafick Pierre

doi:10.1002/j.1460-2075.1994.tb06320.x

Cited by 68 publications

(61 citation statements)

References 61 publications

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“…Moreover, in the COS-7 cell reconstitution system, we show that CD4 dimers can be observed in the absence of p56 lck and that a mutant CD4 that fails to associate with p56 lck retains its dimerization ability (Fig. 1C) (45). Similar findings have been previously reported by Lynch et al (17) using peptides encompassing sequences within the cytoplasmic portion of CD4.…”

Section: Discussionsupporting

confidence: 90%

CD4 Dimers Constitute the Functional Component Required for T Cell Activation

Moldovan

Yachou

Lévesque³

et al. 2002

The Journal of Immunology

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The CD4 molecule plays a key role in the development and activation of helper T cells. Dimerization and oligomerization is often a necessary step in the function of several cell surface receptors. Herein, we provide direct biochemical evidence confirming the presence of CD4 as dimers in transfected cells from hemopoetic and fibroblastic origin as well as in primary T cells. Such dimers are also observed with murine CD4 confirming selective pressure during evolution to maintain such a structure. Using a series of point mutations, we have precisely mapped the dimerization site at residues K318 and Q344 within the fourth extracellular domain of CD4. These residues are highly conserved and their mutation results in interference with dimer formation. More importantly, we demonstrate that dimer formation is essential for the coligand and coreceptor functions of CD4 in T cell activation. These data strongly suggest that CD4 dimerization is necessary for helper T cell function.

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Section: Discussionsupporting

confidence: 90%

CD4 Dimers Constitute the Functional Component Required for T Cell Activation

Moldovan

Yachou

Lévesque³

et al. 2002

The Journal of Immunology

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“…In addition, the observation that F97-6B3 mAb inhibited virus entry as well as OKB7 Ab suggests that other sites than SRC 1 and 2 are involved in the interactions between HIV and CRs. Inhibition of opsonized HIV infection by CD21 reagents have also been described in T cell lines [18,28], B cell lines [22][23][24] and thymocytes [25]. On B cell lines, Tremblay et al [22] have obtained a complete inhibition of the C'-ADE HIV infection with OKB7 whereas this antibody only induced a partial one in our normal B cells.…”

Section: Discussionmentioning

confidence: 68%

“…Inhibition of opsonized HIV infection by CD21 reagents have also been described in T cell lines [18,28], B cell lines [22][23][24] and thymocytes [25]. On B cell lines, Tremblay et al [22] have obtained a complete inhibition of the C'-ADE HIV infection with OKB7 whereas this antibody only induced a partial one in our normal B cells. In these cells as well as in thymocytes [32], CD35 synergize with CD21 for the blocking of HIV entry.…”

Section: Discussionmentioning

confidence: 68%

“…In spite of this activation and of virus opsonization, with anti-HIV antibodies and complement or complement only, HIV seems to be protected from human complement lytic action [17,10]. Non-lysed opsonized HIV may, thus, bind to complement receptors and infect CRs-bearing cells, as described on T cell lines [18], monocytic cell lines [19 21], B cell lines [22][23][24], thymocytes [25], primary monocytes [21], peripheral and tonsil B lymphocytes [8].…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms of opsonized HIV entry in normal B lymphocytes

Legendre¹,

Gras²,

Krzysiek

et al. 1996

FEBS Letters

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Using our in vitro model of normal B cell infection that functions with low doses of HIV but requires virus opsonization by seropositive patient serum, and complement, we analyzed what receptors allowed virus entry. Here, we show that HIV infection of B cells occurs through 2 major receptors: the CD4 antigen and the CRIICR2 complex. These 2 pathways work independently since a complete inhibition of virus entry requires both CD4 and CD211CD35 blockade on CD4 d~ tonsiHar B cells whereas only the latter is critical on CD4-negative B cells.

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“…17 Raji-CD4 cells stably expressing DCIR were obtained following retroviral transduction. In brief, wild-type cDNA encoding for human DCIR was subcloned in the bicistronic retroviral vector MSCV-IRES-eGFP.…”

Section: Cells and Flow Cytometric Analysismentioning

confidence: 99%

DCIR-mediated enhancement of HIV-1 infection requires the ITIM-associated signal transduction pathway

Lambert

Barabé

Gilbert

et al. 2011

Blood

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Dendritic cell immunoreceptor (DCIR) is IntroductionIt is known that cell-free virions do not efficiently cross genital epithelial cells. Instead HIV-1 uses primarily dendritic cells (DCs) to penetrate the mucosal epithelium. 1,2 The virus is then transferred and disseminated from this entry site to T-cell zones in secondary lymphoid organs, where it can productively infect residing CD4 ϩ T cells. The infection process causes a marked depletion of CD4 ϩ T cells, 3 progressive impairment of the immune system, as well as chronic hyperactivation of both CD4 ϩ and CD8 ϩ T cells. 4 The initial attachment step of HIV-1 to DCs may occur through several complex interactions between the virus and the target cell surface (reviewed in Clapham and McKnight 5 and in Ugolini et al 6 ) such as the association between the oligosaccharides found on the external envelope glycoprotein gp120 and the mannose receptor (CD206), langerin (CD207), or 8 This will result in virus capture and transmission to CD4 ϩ T cells in an effective trans mode 9 (ie, transfer of virions bound onto DCs and/or localized in endosomes). Another lectin receptor, that is, the dendritic cell immunoreceptor (DCIR), can behave as an HIV-1 attachment factor for HIV-1 to participate actively in trans infection of CD4 ϩ T cells. 10 DCIR also contributes to cis-infection events, that is, infection of surrounding CD4 ϩ T cells by virions produced by DCs productively infected with HIV-1. 10 DCIR is a member of a recently described family of C-type lectin receptors (CLRs), which includes DCAR, dectin-2, BDCA-2, MCL, and MINCLE. These receptors carry a single carbohydrate recognition domain (CRD) at the COOH terminal and generally lack consensus signaling motifs in their cytoplasmic region. 11 Several members of the family, however, possess a positively charged residue in their transmembrane region, via which they associate with immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptor molecules, such as the Fc receptor ␥ chains. Importantly, DCIR is the only family member harboring an immunoreceptor tyrosine-based inhibitory motif (ITIM), which is involved in modulation of cellular responses. 12 DCIR is expressed on the surface of most antigen-presenting cells (ie DCs, monocytes, macrophages, and B cells), as well as on granulocytes, and it is differentially expressed depending on the DC maturation status. 13 Lipopolysaccharide, IL-4, and TNF-␣ down-regulate DCIR expression on neutrophils. 14 The ITIM domain of DCIR contains the consensus sequence S/I/V/LxYxxI/V/L, including a tyrosine residue at position 7 (ie, ITYAEV). 13 Generally, when ITIM-containing receptors are engaged, they become tyrosine-phosphorylated and then transmit signals by binding and activating Src homology-2 domain (SH2)-containing tyrosine phosphatases (eg, SHP-1 and SHP-2) and/or the SH2-containing tyrosine inositol phosphate (SHIP). 15 In the case of DCIR, one study has demonstrated that, when phosphorylated, it recruits both SHP-1 and SHP-2. 16 Nevertheless, there is still no e...

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Association of p56lck with the cytoplasmic domain of CD4 modulates HIV-1 expression.

Cited by 68 publications

References 61 publications

CD4 Dimers Constitute the Functional Component Required for T Cell Activation

CD4 Dimers Constitute the Functional Component Required for T Cell Activation

Mechanisms of opsonized HIV entry in normal B lymphocytes

DCIR-mediated enhancement of HIV-1 infection requires the ITIM-associated signal transduction pathway

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