M1 polarization of human monocyte-derived macrophages restricts pre and postintegration steps of HIV-1 replication

Cassetta, Luca; Kajaste‐Rudnitski, Anna; Coradin, Tiziana; Saba, Elisa; Chiara, Giulia Della; Barbagallo, Marialuisa; Graziano, Francesca; Alfano, Massimo; Cassol, Edana; Vicenzi, Elisa; Poli, Guido

doi:10.1097/qad.0b013e328361d059

Cited by 57 publications

(62 citation statements)

References 38 publications

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“…Contradictory in vitro evidence indicated that both M1-and M2-polarized macrophages can restrain HIV infection. However, M1 polarization appears the most powerful antiviral program, inhibiting virus entry and replication at pre-and post-integration levels, limiting virus spreading and enhancing activation of adaptive immunity [131,134]. An M1 toward M2 polarization switch of circulating monocytes occurs during the transition from early to late phases of HIV infection, which might support the establishment of chronic latent infection [135].…”

Section: Hiv Infectionmentioning

confidence: 99%

Macrophage polarization in pathology

Sica

Erreni

Allavena

et al. 2015

Cell. Mol. Life Sci.

551

422

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Macrophages are cells of the innate immunity constituting the mononuclear phagocyte system and endowed with remarkable different roles essential for defense mechanisms, development of tissues, and homeostasis. They derive from hematopoietic precursors and since the early steps of fetal life populate peripheral tissues, a process continuing throughout adult life. Although present essentially in every organ/tissue, macrophages are more abundant in the gastro-intestinal tract, liver, spleen, upper airways, and brain. They have phagocytic and bactericidal activity and produce inflammatory cytokines that are important to drive adaptive immune responses. Macrophage functions are settled in response to microenvironmental signals, which drive the acquisition of polarized programs, whose extremes are simplified in the M1 and M2 dichotomy. Functional skewing of monocyte/macrophage polarization occurs in physiological conditions (e.g., ontogenesis and pregnancy), as well as in pathology (allergic and chronic inflammation, tissue repair, infection, and cancer) and is now considered a key determinant of disease development and/or regression. Here, we will review evidence supporting a dynamic skewing of macrophage functions in disease, which may provide a basis for macrophage-centered therapeutic strategies.

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Section: Hiv Infectionmentioning

confidence: 99%

Macrophage polarization in pathology

Sica

Erreni

Allavena

et al. 2015

Cell. Mol. Life Sci.

551

422

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“…To investigate whether human primary macrophages express APOL1, PBMC were isolated from the buffy coats of healthy blood donors and monocytes were isolated by plastic adherence and differentiated for 7 days into monocytederived macrophages (MDM) (17,19,44). MDM from the first donor were either left untreated or stimulated for 18 h with 2 different doses (25 or 50 ng/ml) of IFN-␥ to polarize MDM into macrophages displaying the M1 phenotype (17,19,44). The expression of APOL1 was detected only in MDM stimulated with IFN-␥ and not in resting MDM or PBMC (Fig.…”

Section: Apol1 Stimulates Lysosomal Biogenesis By Promoting Nuclear Lmentioning

confidence: 99%

“…The fact that APOL1 levels are strongly increased in IFN-␥-polarized M1 macrophages that effectively restrict productive HIV-1 infection (17)(18)(19) prompted us to investigate whether APOL1 affects HIV-1 replication.…”

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confidence: 99%

The Innate Immune Factor Apolipoprotein L1 Restricts HIV-1 Infection

Taylor

Khatua

Popik

2014

J Virol

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b Apolipoprotein L1 (APOL1) is a major component of the human innate immune response against African trypanosomes. Although the mechanism of the trypanolytic activity of circulating APOL1 has been recently clarified, the intracellular function(s) of APOL1 in human cells remains poorly defined. Like that of many genes linked to host immunity, APOL1 expression is induced by proinflammatory cytokines gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣). Additionally, IFN-␥-polarized macrophages that potently restrict HIV-1 replication express APOL1, which suggests that APOL1 may contribute to HIV-1 suppression. Here, we report that APOL1 inhibits HIV-1 replication by multiple mechanisms. We found that APOL1 protein targeted HIV-1 Gag for degradation by the endolysosomal pathway. Interestingly, we found that APOL1 stimulated both endocytosis and lysosomal biogenesis by promoting nuclear localization of transcription factor EB (TFEB) and expression of TFEB target genes. Moreover, we demonstrated that APOL1 depletes cellular viral accessory protein Vif, which counteracts the host restriction factor APOBEC3G, via a pathway involving degradation of Vif in lysosomes and by secretion of Vif in microvesicles. As a result of Vif depletion by APOL1, APOBEC3G was not degraded and reduced infectivity of progeny virions. In support of this model, we also showed that endogenous expression of APOL1 in differentiated U937 monocytic cells stimulated with IFN-␥ resulted in a reduced production of virus particles. This finding supports the hypothesis that induction of APOL1 contributes to HIV-1 suppression in differentiated monocytes. Deciphering the precise mechanism of APOL1-mediated HIV-1 restriction may facilitate the design of unique therapeutics to target HIV-1 replication.

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“…We and others have previously shown that cytokine-mediated activation of macrophages results in inhibition of HIV-1 replication at different stages of the replication cycle: in IL-4 activated macrophages, HIV-1 is inhibited at the level of reverse transcription, whereas IFNγþ TNFα and IL-10 stimulation leads to restriction of later stages in the replication cycle (Cassetta et al, 2013;Cassol et al, 2009;Cobos Jiménez et al, 2012). Several new cellular factors have been identified to restrict early steps of HIV-1 replication upon type 1 interferon stimulation of Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/yviro macrophages, such as MX2 (Goujonet al, 2013), IFI16 (Jakobsen et al, 2013) and SAMHD1 (Hrecka et al, 2011;Laguette et al, 2011;Lahouassaet al, 2012), or MCPIP1 in activated CD4 þ T cells (Liu et al, 2013).…”

Section: Introductionmentioning

confidence: 94%

G3BP1 restricts HIV-1 replication in macrophages and T-cells by sequestering viral RNA

et al. 2015

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HIV-1 exploits the cellular machinery for replication and therefore several interactions with cellular factors take place, some of which are yet unknown. We identified GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) as a cellular factor that restricts HIV-1, by analyzing transcriptome profiles of in vitro-cytokine-activated macrophages that are non-permissive to HIV-1 replication. Silencing of G3BP1 by RNA interference resulted in increased HIV-1 replication in primary T-cells and macrophages, but did not affect replication of other retroviruses. G3BP1 specifically interacted with HIV-1 RNA in the cytoplasm, suggesting that it sequesters viral transcripts, thus preventing translation or packaging. G3BP1 was highly expressed in resting naïve or memory T-cells from healthy donors and HIV-1 infected patients, but significantly lower in IL-2-activated T-cells. These results strongly suggest that G3BP1 captures HIV-1 RNA transcripts and thereby restricts mRNA translation, viral protein production and virus particle formation.

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M1 polarization of human monocyte-derived macrophages restricts pre and postintegration steps of HIV-1 replication

Abstract: M1 polarization of in-vitro differentiated primary MDM determines a transient, but profound restriction of HIV-1 replication affecting multiple (entry and postentry) steps in the virus life cycle likely involving the upregulated expression of APOBEC3A.

Cited by 57 publications

References 38 publications

Macrophage polarization in pathology

Macrophage polarization in pathology

The Innate Immune Factor Apolipoprotein L1 Restricts HIV-1 Infection

G3BP1 restricts HIV-1 replication in macrophages and T-cells by sequestering viral RNA

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