Variations in CD4 Expression by Human Monocytes and Macrophages and Their Relationship to Infection with the Human Immunodeficiency Virus

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.

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Fc receptors for IgG (Fc gamma Rs) on human monocytes and macrophages are not infectivity receptors for human immunodeficiency virus type 1 (HIV-1): studies using bispecific antibodies to target HIV-1 to various myeloid cell surface molecules, including the Fc gamma R.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.88.21.9593 ◽

1991 ◽

Vol 88 (21) ◽

pp. 9593-9597 ◽

Cited By ~ 28

Author(s):

R. I. Connor ◽

N. B. Dinces ◽

A. L. Howell ◽

J. L. Romet-Lemonne ◽

J. L. Pasquali ◽

...

Keyword(s):

Myeloid Cell ◽

Bispecific Antibodies ◽

Cell Surface Molecules ◽

Human Monocytes ◽

Surface Molecules ◽

Immunodeficiency Virus ◽

Monocytes And Macrophages ◽

Human Monocytes And Macrophages ◽

Hiv 1

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

Journal of Virology ◽

10.1128/jvi.73.5.3893-3903.1999 ◽

1999 ◽

Vol 73 (5) ◽

pp. 3893-3903 ◽

Cited By ~ 23

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.

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