Myelomonocytic Cell Lines in Modeling HIV-1 Infection of the Bone Marrow

Abstract

Human immunodeficiency virus type 1 (HIV-1), the etiologic agent of acquired immunodeficiency syndrome (AIDS), primarily infects T cells and cells of the monocyte-macrophage lineage. This is due to the presence of the cell surface receptor CD4 and the coreceptors, CXCR4, and CCR5. While the T-cell has classically been the cell type associated with HIV-1 disease progression, cells of the monocyte-macrophage lineage have also been shown to play a major role in this viral pathologic process. Classically, this has involved monocytic cells in the peripheral blood and tissue macrophages, however, over the course of HIV disease, the promyelomonocytic cells of the bone marrow (BM) have also been shown to play a role in pathogenesis retroviral disease in that they play an integral role in the reseeding of the periphery and end-organ tissues. This has involved an initial infection of the bone marrow hematopoietic progenitor cells. Given this observation, over the years there have been a number of cell lines that have been developed and provided valuable insights into research questions surrounding HIV-1 infection of the monocyte-macrophage cell lineage. In this regard, we will examine the biological and immunological properties of these BM-derived cell lines with respect to their utility in exploring the pathogenesis of HIV-1 in humans.

RUNX1 Upregulates CENPE to Promote Leukemic Cell Proliferation

“…It is worth noting that, in these top 10 dysregulated cell growth-related pathways, almost all the affected genes are upregulated, only very few were down-regulated ( Supplementary Figure S2C ). These results were consistent with the notion that THP-1 cells had a more active cell growth phenotype than CD34 + cells ( Nonnemacher et al, 2017 ). Since THP-1 cells are monocytic leukemia, to clarify if our finding is caused by different cell types or direct evidence of Runx1 function in leukemia, we further compared THP-1 cells against monocyte.…”

“…Furthermore, THP-1 cells are acute monocytic leukemia cells with hindered differentiation ( Herbert and Heinzelmann, 2016 ). They are at a less mature stage ( Nonnemacher et al, 2017 ) and display a relatively high stemness (CD34 + phenotype) ( Nasser et al, 2021 ). For comparison, we used CD34 + hematopoietic cells.…”

Defining the molecular mechanisms of HIV‐1 Tat secretion: PtdIns(4,5)P2 at the epicenter

“…The investigations discussed in this review were predominantly performed in primary CD4+ T cells and T cell lines. CD4+ T cells are one of the main targets for HIV-1 infection and are the predominant HIV-1-susceptible cell in the periphery 89 . Monocytes and macrophages are also susceptible and permissive to HIV-1 90 .…”

Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy

“…HIV-1 tropism is classified by the co-receptor used by the variant; R5 viral strains utilize the CCR5 CC-chemokine co-receptor, X4 strains utilize the CXCR4 CXC-chemokine co-receptor, and dual-tropic R5X4 variants have the ability to use both co-receptors though with a greater affinity for CCR5 or CXCR4. Strains that are exclusively R5 predominantly infect monocyte-derived macrophages and memory CD4 cells, which are the prime targets of HIV-1 early in infection, while exclusively X4 strains predominate at a later stage and prefer naïve and resting T cells ( 44 , 84 , 89 ). Early infection is predominantly achieved by R5 tropic viruses because of the relatively high surface expression of CCR5 than CXCR4 on CD4+ memory T cells and immature dendritic cells which determines the efficiency of viral entry, as well as a higher affinity for CD4 ( 84 , 90 ).…”