Mechanisms of opsonized HIV entry in normal B lymphocytes

Legendre, Christophe; Gras, Gabriel; Krzysiek, Roman; Galanaud, Pierre; Richard, Yolande; Dormont, Dominique

doi:10.1016/0014-5793(96)00040-3

Cited by 18 publications

(8 citation statements)

References 28 publications

(32 reference statements)

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“…Another possibility is that HIV directly causes alterations in T lymphocytes. This hypothesis is supported by the observation that the virus can infect also B cells probably through two major receptors: CD4 and CD21/ CD35 complex [25]. Moreover, the outer envelope glycoprotein of HIV gp120 functions as a B cell superantigen and triggers polyclonal B cell activation inducing hypergammaglobulinemia and autoantibody production [26].…”

Section: Discussionsupporting

confidence: 54%

“…The presumptive role of CD21 in B cell activation favors this hypothesis, since modulation of CD21 by immune complexes is a probable mechanism of CD21 involvement in B cell activation, and HIV+ patients are known to have polyclonal B cell activation and increased levels of immune complexes and complement breakdown products [33]. Alternatively, the recent observation that HIV infection of B cells probably occurs through CD21 molecule, suggests a specific downmodulation following HIV entry in B lymphocytes [25]. A similar mechanism is probably involved in CD4 downmodulation after T helper cell infection [10].…”

Section: Discussionmentioning

confidence: 89%

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Changes in Antigen Expression on B Lymphocytesduring HIV Inf ection

Ginaldi¹,

Martinis²,

D'Ostilio³

et al. 1998

Pathobiology

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Involvement of the B cell compartment during HIV infection plays an important role in the development of immune deficiency. The aim of this study was the identification of specific antigen expression changes on B lymphocytes in HIV infection as surrogate markers in this cell population of certain functional aspects that could be easily measured. We investigated the level of expression of a series of constitutive surface markers in B lymphocytes (HLA-DR, CD19, CD20, CD21, CD22) from 30 HIV-seropositive adult patients and 20 normal controls. By means of quantitative flow cytometry, we assessed the number of antigen molecules per cell using standard beads to convert fluorescence intensity into antibody-binding capacity (ABC). We correlated these results with disease stage and cellular markers of immune activation. The expression of CD20 was significantly increased when B cells from HIV-infected individuals were compared with those from uninfected subjects. No differences were found in the density expression of HLA-DR on activated CD3+ T cells between HIV+ and HIV– subjects. In contrast, B cells from HIV+ patients showed a significantly lower number of HLA-DR molecules per cell compared to normal controls. A significantly lower number of CD21 molecules per cell was also found on B lymphocytes from HIV+ patients compared to normal controls. No differences in CD19 and CD22 expression levels on B cells between HIV-infected patients and controls were detected. No differences between HIV disease stages were detected for CD19, HLA-DR, CD21 and CD22. In contrast, differences between stages were found for CD20 expression, which showed significant changes in individuals with less than 200 CD4 T cells/µl. The data presented here demonstrate that B lymphocytes of HIV-infected individuals exhibit specific changes in receptor density expression during HIV infection and that these changes are often correlated with progression of disease, as measured by CD4 counts. No correlations were found between the percentages of HLA-DR+ T cells and the ABC values of the B cell markers studied. These antigen expression modulations may contribute to the humoral abnormalities during HIV infection and to the development of severe, recurrent or multiple bacterial infections. Therefore, quantitative flow cytometry may be of value in HIV infection both for clinical and biological studies. The study of antigen density changes on B cells in HIV infection may allow a better understanding of the humoral immune defects observed in these patients and provide insights into the functional defects of B cell compartment in HIV-infected individuals.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 89%

Changes in Antigen Expression on B Lymphocytesduring HIV Inf ection

Ginaldi¹,

Martinis²,

D'Ostilio³

et al. 1998

Pathobiology

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“…Many authors have analyzed the role of complement in HIV infection (5,7,30,31), but to date only a few studies have addressed the adherence of HIV to erythrocytes (6,32,33). Lachgar et al (33) suggested that the Duffy Ag on the membrane of erythrocytes, which is a chemokine receptor, may serve as a binding site for HIV.…”

Section: Discussionmentioning

confidence: 99%

Complement Mediates the Binding of HIV to Erythrocytes

Horáková

Gasser

Sadallah

et al. 2004

The Journal of Immunology

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A fraction of HIV is associated with erythrocytes even when the virus becomes undetectable in plasma under antiretroviral therapy. The aim of the present work was to further characterize this association in vitro. We developed an in vitro model to study the factors involved in the adherence of HIV-1 to erythrocytes. Radiolabeled HIV-1 (HIV) and preformed HIV-1/anti-HIV immune complexes (HIV-IC) were opsonized in various human sera, purified using sucrose density gradient ultracentrifugation, and incubated with human erythrocytes. We observed that, when opsonized in normal human serum, not only HIV-IC, but also HIV, bound to erythrocytes, although the adherence of HIV was lower than that of HIV-IC. The adherence was abolished when the complement system was blocked, but was maintained in hypogammaglobulinemic sera. Complement-deficient sera indicated that both pathways of complement were important for optimal adherence. No adherence was seen in C1q-deficient serum, and the adherence of HIV was reduced when the alternative pathway was blocked using anti-factor D Abs. The adherence could be inhibited by an mAb against complement receptor 1. At supraphysiological concentrations, purified C1q mediated the binding of a small fraction of HIV and HIV-IC to erythrocytes. In conclusion, HIV-IC bound to erythrocytes as other types of IC do when exposed to complement. Of particular interest was that HIV alone bound also to erythrocytes in a complement/complement receptor 1-dependent manner. Thus, erythrocytes may not only deliver HIV-IC to organs susceptible to infection, but free HIV as well. This may play a crucial role in the progression of the primary infection.

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“…Covalent binding of C3 fragments to the viral envelope allows binding of HIV to cells expressing receptors for C3b (complement receptor (CR) 2 1, CD35), iC3b (CR3, CD11b/CD18; CR4, CD11c/ CD18), and C3d, C3dg (CR2, CD21). HIV-1 infection of human lymphocytes and monocytes/macrophages is greatly enhanced by opsonization of the virus with complement (3)(4)(5).…”

mentioning

confidence: 99%

Cutting Edge: Productive HIV-1 Infection of Dendritic Cells via Complement Receptor Type 3 (CR3, CD11b/CD18)

Bajtay

Speth

Erdei

et al. 2004

The Journal of Immunology

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In the present study, we demonstrate that macrophage-tropic HIV-1 opsonized by complement and limited amounts of anti-HIV-IgG causes up to 10-fold higher productive infection of human monocyte-derived dendritic cells than HIV treated with medium or HIV opsonized by Ab only. Enhanced infection is completely abolished by a mAb specific for the ligand-binding site of CD11b (i.e., α-chain of complement receptor 3, receptor for iC3b), proving the importance of complement receptor 3 in this process. Inhibition of complement activation by EDTA also prevents enhanced infection, further demonstrating the role of complement in virus uptake and productive infection. Since HIV is, even in the absence of Abs, regularly opsonized by complement, most probably the above-described mechanism plays a role during in vivo primary infection.

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Mechanisms of opsonized HIV entry in normal B lymphocytes

Cited by 18 publications

References 28 publications

Changes in Antigen Expression on B Lymphocytesduring HIV Inf ection

Changes in Antigen Expression on B Lymphocytesduring HIV Inf ection

Complement Mediates the Binding of HIV to Erythrocytes

Cutting Edge: Productive HIV-1 Infection of Dendritic Cells via Complement Receptor Type 3 (CR3, CD11b/CD18)

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