scholarly journals Human Immunodeficiency Virus gp120 Inhibits Interleukin-12 Secretion by Human Monocytes: An Indirect Interleukin-10–Mediated Effect

Blood ◽  
1997 ◽  
Vol 89 (8) ◽  
pp. 2842-2848 ◽  
Author(s):  
Y. Taoufik ◽  
O. Lantz ◽  
C. Wallon ◽  
A. Charles ◽  
E. Dussaix ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Aureus Strain ◽  
Interleukin 12 ◽  
Similar Data ◽  
Human Monocytes ◽  
Mrna Accumulation ◽  
Immunodeficiency Virus ◽  
Monocytes And Macrophages ◽  
Hiv Gp120

Abstract Interleukin-12 (IL-12), a cytokine with in vitro and in vivo immunomodulatory effects, is produced mostly by activated monocytes and macrophages. To study the effect of human immunodeficiency virus (HIV) infection on IL-12 production, we investigated the expression of IL-12 at mRNA and protein levels by human monocytes preincubated with HIV-gp120. In these conditions, we show that monocytes have a decreased ability to express IL-12 mRNA subunits and to produce IL-12 p40 and bioactive p70 proteins in response to Staphylococcus aureus strain cowan I (SAC). We showed that in human monocyte cultures, HIV-gp120 induces a significant IL-10 synthesis, which in turn inhibits IL-12 subunits mRNA accumulation and protein secretion after SAC-activation. Similar data were obtained with human macrophages. These results suggest that, during HIV infection, gp120 induces in uninfected monocytes and macrophages IL-10/IL-12 disregulation, which can alter immune response.

scholarly journals Iκκ Mediates NF-κB Activation in Human Immunodeficiency Virus-Infected Cells

1999 ◽  
Vol 73 (5) ◽  
pp. 3893-3903 ◽  
Author(s):  
Susana Asin ◽  
Julie A. Taylor ◽  
Sergey Trushin ◽  
Gary Bren ◽  
Carlos V. Paya
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Viral Persistence ◽  
Human Monocytes ◽  
Regulatory Domains ◽  
Immunodeficiency Virus ◽  
Monocytes And Macrophages ◽  
Infected Cells

ABSTRACT Human monocytes and macrophages are persistent reservoirs of human immunodeficiency virus (HIV) type-1. Persistent HIV infection of these cells results in increased levels of NF-κB in the nucleus secondary to increased IκBα, IκBβ, and IκBɛ degradation, a mechanism postulated to regulate viral persistence. To characterize the molecular mechanisms regulating HIV-mediated degradation of IκB, we have sought to identify the regulatory domains of IκBα targeted by HIV infection. Using monocytic cells stably expressing different transdominant molecules of IκBα, we determined that persistent HIV infection of these cells targets the NH2 but not the COOH terminus of IκBα. Further analysis demonstrated that phosphorylation at S32 and S36 is necessary for HIV-dependent IκBα degradation and NF-κB activation. Of the putative N-terminal IκBα kinases, we demonstrated that the Iκκ complex, but not p90 rsk , is activated by HIV infection and mediates HIV-dependent NF-κB activation. Analysis of viral replication in cells that constitutively express IκBα negative transdominant molecules demonstrated a lack of correlation between virus-induced NF-κB (p65/p50) nuclear translocation and degree of viral persistence in human monocytes.

The Interleukin-12–Mediated Pathway of Immune Events Is Dysfunctional in Human Immunodeficiency Virus–Infected Individuals

Blood ◽  
1999 ◽  
Vol 94 (3) ◽  
pp. 1003-1011 ◽  
Author(s):  
Jason D. Marshall ◽  
Jihed Chehimi ◽  
Giorgia Gri ◽  
Jay R. Kostman ◽  
Luis J. Montaner ◽  
...  
Keyword(s):  
Immune Deficiency ◽  
Human Immunodeficiency Virus ◽  
Nk Cells ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Interleukin 12 ◽  
Accessory Cell ◽  
Mrna Accumulation ◽  
Immunodeficiency Virus ◽  
Ifn Γ

Interleukin-12 (IL-12) is a potentially critical factor in the immune response against human immunodeficiency virus (HIV) because it is important for regulating proliferation and interferon-γ (IFN-γ) production by T cells and natural killer (NK) cells, antigen presentation and accessory cell function by macrophages and dendritic cells, and cytolytic activities of cytotoxic T-lymphocyte cells and NK cells, which are all functions known to be dysfunctional in patients with acquired immune deficiency syndrome. Peripheral blood mononuclear cells (PBMC) from HIV-infected patients have been previously shown to be deficient in the ability to produce IL-12 in response to the bacterial pathogen Staphylococcus aureus Cowan. In this study, impaired IL-12 production in cells from PBMC of HIV-infected patients compared with healthy donors was observed across a broad panel of stimuli derived from infectious pathogens with or without priming with cytokines such as IFN-γ and IL-4, which amplify the IL-12 induction signal. Analysis of p40 and p35 mRNA accumulation showed that reductions in both subunits contribute to the lower IL-12 secretion of cells from HIV-infected individuals. PBMC from HIV-infected donors also failed to upregulate the IL-12 receptor β2 chain (IL-12Rβ2) in response to mitogenic stimuli. The expression of the IL-12Rβ2 gene could, however, be restored by in vitro exposure to rIL-12. Thus, it is possible that a primary IL-12 defect may lead to secondary deficiencies in expression of the genes for IL-12Rβ2 and IFN-γ, thus amplifying immune deficiency during HIV infection.

scholarly journals Double-Stranded RNA Analog Poly(I:C) Inhibits Human Immunodeficiency Virus Amplification in Dendritic Cells via Type I Interferon-Mediated Activation of APOBEC3G

2008 ◽  
Vol 83 (2) ◽  
pp. 884-895 ◽  
Author(s):  
Susanna Trapp ◽  
Nina R. Derby ◽  
Rachel Singer ◽  
Andrew Shaw ◽  
Vennansha G. Williams ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
Hiv Infection ◽  
Molecular Mass ◽  
Type I Interferon ◽  
Poly I:C ◽  
Interleukin 12 ◽  
Type I ◽  
Immunodeficiency Virus

ABSTRACT Human immunodeficiency virus (HIV) is taken up by and replicates in immature dendritic cells (imDCs), which can then transfer virus to T cells, amplifying the infection. Strategies known to boost DC function were tested for their ability to overcome this exploitation when added after HIV exposure. Poly(I:C), but not single-stranded RNA (ssRNA) or a standard DC maturation cocktail, elicited type I interferon (IFN) and interleukin-12 (IL-12) p70 production and the appearance of unique small (15- to 20-kDa) fragments of APOBEC3G (A3G) and impeded HIVBal replication in imDCs when added up to 60 h after virus exposure. Comparable effects were mediated by recombinant alpha/beta IFN (IFN-α/β). Neutralizing the anti-IFN-α/β receptor reversed poly(I:C)-induced inhibition of HIV replication and blocked the appearance of the small A3G proteins. The poly(I:C)-induced appearance of small A3G proteins was not accompanied by significant differences in A3G mRNA or A3G monomer expression. Small interfering RNA (siRNA) knockdown of A3G could not be used to reverse the poly(I:C)-induced protective effect, since siRNAs nonspecifically activated the DCs, inducing the appearance of the small A3G proteins and inhibiting HIV infection. Notably, the appearance of small A3G proteins coincided with the shift of high-molecular-mass inactive A3G complexes to the low-molecular-mass (LMM) active A3G complexes. The unique immune stimulation by poly(I:C) with its antiviral effects on imDCs marked by the expression of IFN-α/β and active LMM A3G renders poly(I:C) a promising novel strategy to combat early HIV infection in vivo.

scholarly journals Impaired interleukin 12 production in human immunodeficiency virus-infected patients.

1994 ◽  
Vol 179 (4) ◽  
pp. 1361-1366 ◽  
Author(s):  
J Chehimi ◽  
S E Starr ◽  
I Frank ◽  
A D'Andrea ◽  
X Ma ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Mononuclear Cells ◽  
Biologically Active ◽  
Uninfected Control ◽  
Interleukin 12 ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Immunodeficiency Virus

Peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients, asymptomatic or with acquired immunodeficiency virus, produced 10-fold less interleukin 12 (IL-12) free heavy chain and fivefold less biologically active IL-12 heterodimer than PBMC from uninfected healthy donors when challenged in vitro with the common human pathogen Staphylococcus aureus. In contrast, PBMC from HIV-infected individuals and uninfected control donors produced similar levels of tumor necrosis factor alpha, IL-1 beta, and IL-10, and PBMC from HIV-infected individuals produced three- to fourfold more IL-6 compared with PBMC from uninfected control donors. The defect in IL-12 production is not due to hyperproduction of IL-10, a cytokine exerting an autocrine-negative feedback on IL-12 production, but was directly related to HIV infection, as suggested by the reduced ability of monocytes infected in vitro with HIV to produce IL-12. IL-12 deficiency may be an important component of the immunodeficiency associated with HIV infection.

Human Immunodeficiency Virus (HIV) Infection in Children

1987 ◽  
Vol 1 (3) ◽  
pp. 381-395 ◽  
Author(s):  
Beverly Ryan ◽  
Edward Connor ◽  
Anthony Minnefor ◽  
Frank Desposito ◽  
James Oleske
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Infection ◽  
Immunodeficiency Virus
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