Monocyte-lymphocyte fusion induced by the HIV-1 envelope generates functional heterokaryons with an activated monocyte-like phenotype

Martínez-Méndez, David; Rivera-Toledo, Evelyn; Ortega, Enrique; Licona‐Limón, Ileana; Huerta, Leonor

doi:10.1016/j.yexcr.2017.01.014

Cited by 8 publications

(5 citation statements)

References 59 publications

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“…HIV-1-induced fusion of T cells with macrophages has been evoked as a mode of viral spread between these cell types that may occur in parallel with VS-mediated viral spread [85], similar to the early work by the Steinman lab on DC-T cell syncytium formation driven by HIV-1 infection [32,86]. Env-mediated fusion between monocytic and T cell lines revealed that the ensuing heterokaryons were viable, stable, and presented a dominant activated monocyte-like phenotype [87]. Revisiting the concept of myeloid-T cell fusion more recently [88], coculture between acutely HIV-1-infected activated CD4 + T cells and MDM culminated in the rapid appearance of Gag + multinucleated MDM that expressed phenotypic T cell markers (CD2, CD3, Lck), and which was prevented by HIV-1 fusion inhibitors.…”

Section: Fusion Between Hiv-1-infected Cd4 + T Cells and Macrophagesmentioning

confidence: 81%

Macrophage Cell-Cell Interactions Promoting HIV-1 Infection

Dupont

Sattentau

2020

Viruses

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Many pathogens infect macrophages as part of their intracellular life cycle. This is particularly true for viruses, of which HIV-1 is one of the best studied. HIV-1 infection of macrophages has important consequences for viral persistence and pathogenesis, but the mechanisms of macrophage infection remain to be fully elucidated. Despite expressing viral entry receptors, macrophages are inefficiently infected by cell-free HIV-1 virions, whereas direct cell-cell spread is more efficient. Different modes of cell-cell spread have been described, including the uptake by macrophages of infected T cells and the fusion of infected T cells with macrophages, both leading to macrophage infection. Cell-cell spread can also transmit HIV-1 between macrophages and from macrophages to T cells. Here, we describe the current state of the field concerning the cell-cell spread of HIV-1 to and from macrophages, discuss mechanisms, and highlight potential in vivo relevance.

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Section: Fusion Between Hiv-1-infected Cd4 + T Cells and Macrophagesmentioning

confidence: 81%

Macrophage Cell-Cell Interactions Promoting HIV-1 Infection

Dupont

Sattentau

2020

Viruses

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“…CD4+ T cells were defined as CD3+/CD4+ cells or CD4+/CD8− cells depending on the activation stimulus used. The presence of conjugates between T cells and cells known to express high levels of CD32, such as CD19+ B cells or CD14+ monocytes 21 , was excluded by gating on forward scatter (FSC) singlets and measuring the expression of CD19+ or CD14+ in the CD32+ cells and/or the CD4+ T-cell population (Supplementary Fig. 1a, b ).…”

Section: Resultsmentioning

confidence: 99%

CD32 expression is associated to T-cell activation and is not a marker of the HIV-1 reservoir

et al. 2018

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CD32 has been shown to be preferentially expressed in latently HIV-1-infected cells in an in vitro model of quiescent CD4 T cells. Here we show that stimulation of CD4+ T cells with IL-2, IL-7, PHA, and anti-CD3/CD28 antibodies induces T-cell proliferation, co-expression of CD32 and the activation of the markers HLA-DR and CD69. HIV-1 infection increases CD32 expression. 79.2% of the CD32+/CD4+ T cells from HIV+ individuals under antiretroviral treatment were HLA-DR+. Resting CD4+ T cells infected in vitro generally results in higher integration of provirus. We observe no difference in provirus integration or replication-competent inducible latent HIV-1 in CD32+ or CD32− CD4+ T cells from HIV+ individuals. Our results demonstrate that CD32 expression is a marker of CD4+ T cell activation in HIV+ individuals and raises questions regarding the immune resting status of CD32+ cells harboring HIV-1 proviruses.

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“…Consistent with this hypothesis, in vivo studies have shown that lymphoid tissue-resident macrophages of Simian Immunodeficiency Virus (SIV)-infected macaques contain T-cell markers and viral nucleic acids originating from infected T cells [ 77 , 78 ]. The lack of formal evidence for the existence of these HIV-induced heterokaryons in vivo could be explained by the fact that, in vitro, these lymphocyte-monocyte cells retain a myeloid phenotype and rapidly downregulate T cell markers [ 79 ]. The opposite mechanism ( i.e.…”

Section: Different Types Of Multinucleated Giant Cells From the Monocytic Lineagementioning

confidence: 99%

Cellular and molecular actors of myeloid cell fusion: podosomes and tunneling nanotubes call the tune

Dufrançais

Mascarau

Poincloux

et al. 2021

Cell. Mol. Life Sci.

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Different types of multinucleated giant cells (MGCs) of myeloid origin have been described; osteoclasts are the most extensively studied because of their importance in bone homeostasis. MGCs are formed by cell-to-cell fusion, and most types have been observed in pathological conditions, especially in infectious and non-infectious chronic inflammatory contexts. The precise role of the different MGCs and the mechanisms that govern their formation remain poorly understood, likely due to their heterogeneity. First, we will introduce the main populations of MGCs derived from the monocyte/macrophage lineage. We will then discuss the known molecular actors mediating the early stages of fusion, focusing on cell-surface receptors involved in the cell-to-cell adhesion steps that ultimately lead to multinucleation. Given that cell-to-cell fusion is a complex and well-coordinated process, we will also describe what is currently known about the evolution of F-actin-based structures involved in macrophage fusion, i.e., podosomes, zipper-like structures, and tunneling nanotubes (TNT). Finally, the localization and potential role of the key fusion mediators related to the formation of these F-actin structures will be discussed. This review intends to present the current status of knowledge of the molecular and cellular mechanisms supporting multinucleation of myeloid cells, highlighting the gaps still existing, and contributing to the proposition of potential disease-specific MGC markers and/or therapeutic targets.

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Monocyte-lymphocyte fusion induced by the HIV-1 envelope generates functional heterokaryons with an activated monocyte-like phenotype

Cited by 8 publications

References 59 publications

Macrophage Cell-Cell Interactions Promoting HIV-1 Infection

Macrophage Cell-Cell Interactions Promoting HIV-1 Infection

CD32 expression is associated to T-cell activation and is not a marker of the HIV-1 reservoir

Cellular and molecular actors of myeloid cell fusion: podosomes and tunneling nanotubes call the tune

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