Coreceptor Competition for Association with CD4 May Change the Susceptibility of Human Cells to Infection with T-Tropic and Macrophagetropic Isolates of Human Immunodeficiency Virus Type 1

Lee, Shirley; Lapham, Cheryl; Chen, Hong; King, Lisa R.; Manischewitz, Jody; Romantseva, Tatiana; Mostowski, Howard; Stantchev, Tzanko S.; Broder, Christopher C.; Golding, Hana

doi:10.1128/.74.11.5016-5023.2000

Cited by 4 publications

(3 citation statements)

References 30 publications

(54 reference statements)

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“…For instance one can hypothesize that CD4 is preferentially confined with CCR5 into microdomains different from those containingCXCR4 [22]. This hypothesis is in agreement with the observation that reducing the expression of CD4 decreases the susceptibility of human cells to infection by X4 viruses [46]. Furthermore, it has been shown that lowering CCR5 expression level with molecules modulating cholesterol content (lovastatin, mevastatin and simvastatin), favors the infection by X4 viruses [47].…”

Section: Cxcr4 Co-receptorsupporting

confidence: 78%

Membrane organization of virus and target cell plays a role in HIV entry

2014

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The initial steps of the Human Immunodeficiency Virus (HIV) replication cycle play a crucial role that arbitrates viral tropism and infection efficiency. Before the release of its genome into the host cell cytoplasm, viruses operate a complex sequence of events that take place at the plasma membrane of the target cell. The first step is the binding of the HIV protein envelope (Env) to the cellular receptor CD4. This triggers conformational changes of the gp120 viral protein that allow its interaction with a co-receptor that can be either CCR5 or CXCR4, defining the tropism of the virus entering the cell. This sequential interaction finally drives the fusion of the viral and host cell membrane or to the endocytosis of the viruses. Here, we discuss how the membrane composition and organization of both the virus and the target cell can affect these steps and thus influence the capability of the viruses to infect cells.

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Section: Cxcr4 Co-receptorsupporting

confidence: 78%

Membrane organization of virus and target cell plays a role in HIV entry

2014

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“…40 Other studies show that inefficient interactions of CXCR4 with CD4 and gp120 on macrophages and/or interference of CXCR4/CD4 association when CXCR4 and CCR5 are co-expressed on macrophages reduce fusion and subsequent infection of these cells with X4-using HIV-1. [40][41][42] These interactions may be influenced by unique membrane components of MDM differentiated in M-CSF and/or CXCL4 and could account for the differences in replication of X4 HIV-1. Although we observed human donor variability often reported by others, the pattern of lower replication of CXCR4-using viruses was consistent.…”

Section: Discussionmentioning

confidence: 99%

Platelet factor 4 (CXCL4) facilitates human macrophage infection with HIV-1 and potentiates virus replication

et al. 2009

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Platelet factor 4 (CXCL4), a member of the CXC chemokine subfamily released in high amounts by activated platelets, has been identified as a monocyte survival factor that induces monocyte differentiation into macrophages. Although CXCL4 has been shown to have biological effects unique to chemokines, nothing is known about the role of CXCL4-derived human macrophages or CXCL4 in human immunodeficiency virus (HIV) disease. In this study, CXCL4-derived macrophages are compared with macrophage-colony stimulating factor (M-CSF)-derived macrophages for their ability to support HIV-1 replication. We show that CXCL4-derived macrophages can be infected with macrophage-tropic HIV-1 that uses either CC-chemokine receptor 5 (CCR5) or CXC-chemokine receptor 4 (CXCR4) as a co-receptor for viral entry. We also find that M-CSF and the chemokines, monocyte chemoattractant protein 1 (MCP-1; CCL2) and macrophage-inflammatory-protein-1-alpha (MIP-1alpha; CCL3) are produced upon R5- and X4-tropic HIV-1 replication in both M-CSF- and CXCL4-derived human macrophages. In addition, CXCL4 added to M-CSF-derived macrophages after virus adsorption and maintained throughout the infection enhances HIV-1 replication. We thus propose a novel role for CXCL4 in HIV disease.

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“…Changes in expression and conformation of CXCR4 could affect the susceptibility of a given cell to infection by T-tropic HIV-1 strains, which only use CXCR4 as a coreceptor. Such changes may also indirectly influence infection by M-tropic HIV-1, which uses CCR5 as a coreceptor, as the two coreceptors compete with each other for interaction with CD4 [37]. In addition, changes in conformation may alter the effectiveness of vaccines and small drugs that target the coreceptors.…”

Section: Discussionmentioning

confidence: 99%

CXCR4 heterogeneity in primary cells: possible role of ubiquitination

Lapham

Romantseva

Petricoin

et al. 2002

Journal of Leukocyte Biology

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The chemokine receptor CXCR4 is a primary coreceptor for the HIV-1 virus. The predicted molecular weight (MW) of glycosylated CXCR4 is 45–47 kDa. However, immunoblots of whole cell lysates from human lymphocytes, monocytes, macrophages, and the Jurkat T-lymphocyte line revealed multiple MW isoforms of CXCR4. Three of the bands could be precipitated by anti-CXCR4 monoclonal antibodies (101 and 47 kDa) or coprecipitated with CD4 (62 kDa). Expression of these isoforms was enhanced by infection with a recombinant vaccinia virus encoding CXCR4. In immunoblots of two-dimensional gels, antiubiquitin antibodies reacted with the 62-kDa CXCR4 species from monocytes subsequent to coprecipitation with anti-CD4 antibodies. Culturing of monocytes and lymphocytes with lactacystin enhanced the amount of the 101-kDa CXCR4 isoform in immunoblots by three- to sevenfold. In lymphocytes, lactacystin also increased cell-surface expression of CXCR4, which correlated with enhanced fusion with HIV-1 envelope-expressing cells. Similar increases in the intensity of the 101-kDa isoform were seen after treatment with the lysosomal inhibitors monensin and ammonium chloride. Antiubiquitin antibodies reacted with multiple proteins above 62 kDa, which were precipitated with anti-CXCR4 antibodies. Our data indicate that ubiquitination may contribute to CXCR4 heterogeneity and suggest roles for proteasomes and lysosomes in the constitutive turnover of CXCR4 in primary human cells.

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Coreceptor Competition for Association with CD4 May Change the Susceptibility of Human Cells to Infection with T-Tropic and Macrophagetropic Isolates of Human Immunodeficiency Virus Type 1

Cited by 4 publications

References 30 publications

Membrane organization of virus and target cell plays a role in HIV entry

Membrane organization of virus and target cell plays a role in HIV entry

Platelet factor 4 (CXCL4) facilitates human macrophage infection with HIV-1 and potentiates virus replication

CXCR4 heterogeneity in primary cells: possible role of ubiquitination

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