HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages

Swingler, Simon; Mann, Angela M.; Jacqué, Jean Marc; Břicháček, Beda; Sasseville, Vito G.; Williams, Ken; Lackner, Andrew A.; Janoff, Edward N.; Wang, R.; Fisher, Daniel; Stevenson, Mario

doi:10.1038/12433

Cited by 337 publications

(278 citation statements)

References 52 publications

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“…Similar to our findings with M-CSF, MIP-1␣ production by HIV-1-infected MDM is also dependent on viral replication (27,28), but it is not specific for HIV-1. Intriguingly, it has recently been shown that production of MIP-1␣, but not M-CSF, is regulated by the HIV-1 nef protein (34). A role for HIV accessory proteins in the regulation of M-CSF production has yet to be defined and is currently under investigation in our laboratory.…”

Section: Discussionmentioning

confidence: 99%

Macrophage Colony-Stimulating Factor Antagonists Inhibit Replication of HIV-1 in Human Macrophages

Kutza

Crim

Feldman

et al. 2000

The Journal of Immunology

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Macrophages infected with HIV-1 produce high levels of M-CSF and macrophage-inflammatory protein-1α (MIP-1α). M-CSF facilitates the growth and differentiation of macrophages, while the chemotactic properties of MIP-1α attract both T lymphocytes and macrophages to the site of HIV infection. Studies described in this work indicate M-CSF may function in an autocrine/paracrine manner to sustain HIV replication, and data suggest possible therapeutic strategies for decreasing viral load following HIV infection. We show that macrophage infection with measles virus or respiratory syncytial virus, in contrast to HIV-1, results in production of MIP-1α, but not M-CSF. Thus, M-CSF appears to be specifically produced upon infection of macrophages with HIV-1. Furthermore, addition of M-CSF antagonists to HIV-1-infected macrophages, including anti-M-CSF monoclonal or polyclonal Abs or soluble M-CSF receptors, dramatically inhibited HIV-1 replication and reduced production of MIP-1α. Our results suggest that biologic antagonists for M-CSF may represent novel strategies for inhibiting the spread of HIV-1 by 1) blocking virus replication in macrophages, 2) reducing recruitment of HIV-susceptible T cells and macrophages by MIP-1α, and 3) preventing the establishment and maintenance of infected macrophages as a reservoir for HIV.

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Section: Discussionmentioning

confidence: 99%

Macrophage Colony-Stimulating Factor Antagonists Inhibit Replication of HIV-1 in Human Macrophages

Kutza

Crim

Feldman

et al. 2000

The Journal of Immunology

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“…Nef is a 27-kDa protein that is produced early during infection and exerts multiple functional activities. The expression of Nef induces the secretion of CC-chemokines MIP-1 and MIP-1 by infected macrophages (Swingler et al, 1999). These chemokines may help to recruit T lymphocytes at the site of infection by chemotaxis.…”

Section: Macrophage-t Cell Interplay and Hiv-1 Activationmentioning

confidence: 99%

“…These chemokines may help to recruit T lymphocytes at the site of infection by chemotaxis. Moreover, T lymphocytes are activated by a soluble factor released by Nef-expressing macrophages, favouring HIV-1 replication (Swingler et al, 1999). Further studies by the same laboratory showed that CD40L stimulation of macrophages also leads to the release of a factor that induces T lymphocytes to support the replication of an X4 strain of HIV-1 without any other extrinsic stimulation (Swingler et al, 2003).…”

Section: Macrophage-t Cell Interplay and Hiv-1 Activationmentioning

confidence: 99%

Macrophages and HIV-1: dangerous liaisons

Verani¹,

Gras

Pancino

2005

Molecular Immunology

102

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“…The lymphocyte chemotaxis assay was performed using 96-well microchemotaxis chambers (NeuroProbe, Gaithersburg, MD) as previously described (28). The MACS magnetic cell separation system was used to isolate CD8 ϩ T cells from fresh PBMCs taken from healthy individuals.…”

Section: Lymphocyte Chemotaxis Assaymentioning

confidence: 99%

Functional Expression of the Chemokine Receptor CCR5 on Virus Epitope-Specific Memory and Effector CD8+ T Cells

Fukada

Sobao

Tomiyama

et al. 2002

The Journal of Immunology

109

117

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Because the chemokine receptor CCR5 is expressed on Th1 CD4+ cells, it is important to investigate the expression and function of this receptor on other T cells involved in Th1 immune responses, such as Ag-specific CD8+ T cells, which to date have been only partially characterized. Therefore, we analyzed the expression and function of CCR5 on virus-specific CD8+ T cells identified by HLA class I tetramers. Multicolor flow cytometry analysis demonstrated that CCR5 is expressed on memory (CD28+CD45RA−) and effector (CD28−CD45RA− and CD28−CD45RA+) CD8+ T cells but not on naive (CD28+CD45RA+) CD8+ T cells. CCR5 expression was much lower on two effector CD8+ T cells than on memory CD8+ T cells. Analysis of CCR7 and CCR5 expression on the different types of CD8+ T cells showed that memory CD8+ T cells have three phenotypic subsets, CCR5+CCR7−, CCR5+CCR7+, and CCR5−CCR7+, while naive and effector CD8+ T cells have CCR5−CCR7+ and CCR5+CCR7− phenotypes, respectively. These results suggest the following sequence for differentiation of memory CD8+ T cells: CCR5−CCR7+→CCR5+CCR7+→CCR5+CCR7−. CCR5+CD8+ T cells effectively migrated in response to RANTES, suggesting that CCR5 plays a critical role in the migration of Ag-specific effector and differentiated memory CD8+ T cells to inflammatory tissues and secondary lymphoid tissues. This is in contrast to CCR7, which functions as a homing receptor in migration of naive and memory CD8+ T cells to secondary lymphoid tissues.

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HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages

Cited by 337 publications

References 52 publications

Macrophage Colony-Stimulating Factor Antagonists Inhibit Replication of HIV-1 in Human Macrophages

Macrophage Colony-Stimulating Factor Antagonists Inhibit Replication of HIV-1 in Human Macrophages

Macrophages and HIV-1: dangerous liaisons

Functional Expression of the Chemokine Receptor CCR5 on Virus Epitope-Specific Memory and Effector CD8+ T Cells

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