The susceptibility of macrophages to human immunodeficiency virus type 1 X4 isolates dependson their activation state

doi:10.1016/S0753-3322(00)00015-9

Biomedicine & Pharmacotherapy

Volume 55, Issue 1, February 2001, Pages 32-38

https://doi.org/10.1016/S0753-3322(00)00015-9 Get rights and content

Abstract

The demonstration that macrophages express CXCR4 has led to a reexamination of their susceptibility to human immunodeficiency (HIV)-1 X4 strains. Here, we examined the susceptibility to X4 HIV-1Lai of two previously characterized macrophage populations, obtained either as 1) adherent cells of five-day cultures of blood mononuclear cells (PBMC), followed by two days without nonadherent PBMC nor added cytokines (MDM-5d); or 2) as adherent cells recovered from one-hour incubation of PBMC, which were cultured for seven days with macrophage colony-stimulating factor (MDM-MCSF). Exposing MDM-5d or MDM-MCSF to HIV-1Lai did not lead to productive infection, as indicated by a lack of (MDM-MCSF) or low (MDM-5d) viral p24 levels in culture supernatants. However, MDM-5d vigorously transmitted HIV-1Lai to autologous T lymphocytes, which was not the case of HIV-1Lai-exposed MDM-MCSF. PCR analysis of the LTR RU5 region showed that X4 HIV-1Lai entered into both types of macrophages in the same manner as R5 HIV-1BaL. However, in contrast to MDM-5d, there was a block of HIV-1Lai retrotransciption in MDM-MCSF. Cytokine profile analysis of the two types of macrophages showed that TNF-α, IL-6 and RANTES levels were higher in MDM-5d than in MDM-MSCF, while the IL10 level was higher in MDM-MCSF, both producing similar IL16 levels. Altogether, these data indicate that HIV-1 X4 strains enter into macrophages but that their replication is blocked thereafter in a different manner according to the activation status of the cells.

Section snippets

Reagents

Recombinant human macrophage colony-stimulating factor (M-CSF) was from R&D Systems (Minneapolis, MN). Monoclonal antibodies (mAbs) CD4 (phycoerythrin [PE]-Leu3a), CD14 (fluorescein isothiocyanate [FITC]-LeuM3) were from Becton-Dickinson (Mountain View, CA). Anti-CCR5, -CCR3 and -CXCR4 mAbs were from the NIH AIDS Reagent Program (Bethesda, MD) or from R&D Systems.

Cells

Buffy-coat peripheral blood mononuclear cells (PBMC) from healthy donors were isolated by Ficoll-Paque (Pharmacia, Uppsala, Sweden)

Susceptiblity of monocyte-derived macrophages to HIV-1Lai/X4 isolate

As reported, macrophages generated under either condition, i.e., MDM-5d or MDM-MCSF, expressed comparable CXCR4 and CCR5 levels [1]. Here, we analysed the susceptibilty of these two macrophage populations to X4 HIV-1Lai infection. Exposure of MDM-MCSF to 500 TCID50 HIV-1Lai did not result in production of detectable p24 in supernatants (figure 1), even over three to four weeks of culture (data not shown). HIV-1Lai-exposed MDM-5d produced p24 that did not exceed 200 pg/mL (i.e., 500- to

Discussion

Macrophages are important targets of HIV-1 in vivo and serve as reservoirs for viral persistence. In fact, macrophages express CD4, CCR5, and CXCR4 1, 7, 27, but the ability of macrophage chemokine receptors to support HIV-1 entry and infection is both cell- and strain-specific. Actually, it has been described that macrophages are permissive for R5 and dual-tropic R5X4 viruses but not for X4 strains 7, 23, 27. Recent data showed that this restricted susceptibility of macrophages to such strains

Acknowledgements

We thank Birgitta Äsjo (Bergen, Norway) for the gift of HIV-1BaL, and the NIH AIDS Reagent Program (Bethesda, MD) for providing anti-CCR5, -CCR3 and -CXCR4 mAbs. This work was supported by the Agence Nationale de Recherche sur le SIDA (ANRS), Ensemble contre le SIDA - Sidaction, and the Moroccan Programme d’Appui à la Recherche Scientifique (PARS). YB is the recipient of a predoctoral fellowship from ANRS.

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Dossier: AIDSThe susceptibility of macrophages to human immunodeficiency virus type 1 X4 isolates dependson their activation state

Abstract

Section snippets

Reagents

Cells

Susceptiblity of monocyte-derived macrophages to HIV-1Lai/X4 isolate

Discussion

Acknowledgements

Virology

Blood

Res Immunol

Virology

Biomed Pharmacother

HIV’s other immune-system targets: macrophages

Science

Inactivation of HIV-1 chemokine co-receptor CXCR-4 by a novel intrakine strategy

Nat M

Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy

Proc Natl Acad Sci USA

Host factors in the pathogenesis of the HIV disease

Immunol Rev

Cofactors for human immunodeficiency virus entry into primary macrophages

J Infect Dis

Change in coreceptor use correlates with disease progression in HIV-1-infected individuals

J Exp M

Chemokine receptor regulation and HIV type 1 tropism in monocyte- macrophages

AIDS Res Hum Retroviruses

Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat

Proc Natl Acad Sci USA

Enhancement of human immunodeficiency virus type 1 infection by the CC-chemokine RANTES is independent of the mechanism of virus-cell fusion

J Virol

Restricted HIV type 1 replication under serum-free culture conditions in human monocyte-derived macrophages

AIDS Res Hum Retroviruses

Dossier: AIDS
The susceptibility of macrophages to human immunodeficiency virus type 1 X4 isolates dependson their activation state