Human immunodeficiency virus type 1 (HIV-1) Nef activates STAT3 in primary human monocyte/macrophages through the release of soluble factors: involvement of Nef domains interacting with the cell endocytotic machinery

ABSTRACT Increased kynurenine pathway metabolism has been implicated in the etiology of AIDS dementia complex (ADC). The rate-limiting enzyme for this pathway is indolamine 2,3-dioxygenase (IDO). We tested the efficacy of different strains of human immunodeficiency virus type 1 (HIV1-BaL, HIV1-JRFL, and HIV1-631) to induce IDO in cultured human monocyte-derived macrophages (MDM). A significant increase in both IDO protein and kynurenine synthesis was observed after 48 h in MDM infected with the brain-derived HIV-1 isolates, laboratory-adapted (LA) HIV1-JRFL, and primary isolate HIV1-631. In contrast, almost no kynurenine production or IDO protein was evident in MDM infected with the highly replicating macrophage-tropic LA strain HIV1-BaL. The induction of IDO and kynurenine synthesis by HIV1-JRFL and HIV1-631 declined to baseline levels by day 8 postinfection. Abundant HIV-1 replication did not reduce the ability of exogenous gamma interferon (IFN-γ) to induce IDO and kynurenine synthesis in HIV-infected MDM. The addition of anti-IFN-γ antibody to MDM infected with HIV1-JRFL resulted in an absence of detectable IDO protein after 48 h and a decrease of 64% ± 1% in supernatant kynurenine concentration. Together, these results indicate that only selected strains of HIV-1 are capable of inducing IDO synthesis and subsequent kynurenine metabolism in MDM. The induction of IDO, while apparently independent of replication capacity, appears to be mediated by a transient production of IFN-γ in MDM responding to the initial infection with selected strains of HIV-1.

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In primary human monocyte-derived macrophages exposed to Human immunodeficiency virus type 1, does the increased intracellular growth of Leishmania infantum rely on its enhanced uptake?

Journal of General Virology ◽

10.1099/vir.0.81647-0 ◽

2006 ◽

Vol 87 (5) ◽

pp. 1295-1302 ◽

Cited By ~ 18

Author(s):

Chenqi Zhao ◽

Sandra Thibault ◽

Nadine Messier ◽

Marc Ouellette ◽

Barbara Papadopoulou ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Leishmania Infantum ◽

Luciferase Activity ◽

Human Monocyte ◽

Human Beings ◽

Immunodeficiency Virus ◽

Hiv 1

Concurrent uncontrolled development of human immunodeficiency virus type 1 (HIV-1) and Leishmania spp. is regarded as an emerging pathogenic combination in countries where human beings are exposed to these two micro-organisms. The present study was aimed at exploring whether HIV-1 development within a culture of human monocyte-derived macrophages (MDMs) affected the further development of luciferase-encoding Leishmania infantum using the luciferase activity as a readout assay. It was demonstrated that, in cultures of HIV-1-loaded MDMs exposed to axenic amastigotes, the luciferase activity was higher than in HIV-1-free MDMs. As a preliminary approach to deciphering the possible mechanism through which HIV-1 can affect Leishmania infantum, attention was focused on the very early processes that could underlie this increased luciferase activity. Using GFP-labelled parasites, it was possible to establish that, in HIV-1-infected MDMs, the percentage of GFP-expressing MDMs was higher (10–20 %) than in cell cultures not exposed to HIV-1 (5 %). Two-colour immunofluorescence staining suggested that HIV-1 indirectly affects the uptake of parasites inside MDMs. Thus, the observed phenomenon seems to be linked with a higher uptake of parasites within MDMs. Taken together, the data reported here may contribute to our understanding of disseminated Leishmania infection in HIV-1-infected individuals.

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Reversible Human Immunodeficiency Virus Type-1 Latency in Primary Human Monocyte-Derived Macrophages Induced by Sustained M1 Polarization

Scientific Reports ◽

10.1038/s41598-018-32451-w ◽

2018 ◽

Vol 8 (1) ◽

Cited By ~ 4

Author(s):

Francesca Graziano ◽

Giulia Aimola ◽

Greta Forlani ◽

Filippo Turrini ◽

Roberto S. Accolla ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Human Monocyte ◽

Primary Human Monocyte ◽

M1 Polarization ◽

Immunodeficiency Virus

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Impact of the Placental Cytokine-Chemokine Balance on Regulation of Cell-Cell Contact-Induced Human Immunodeficiency Virus Type 1 Translocation across a Trophoblastic Barrier In Vitro

Journal of Virology ◽

10.1128/jvi.79.19.12304-12310.2005 ◽

2005 ◽

Vol 79 (19) ◽

pp. 12304-12310 ◽

Cited By ~ 8

Author(s):

Muriel Derrien ◽

Albert Faye ◽

Guillermina Dolcini ◽

Gérard Chaouat ◽

Françoise Barré-Sinoussi ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Cell Contact ◽

Viral Production ◽

Soluble Factors ◽

Immunodeficiency Virus ◽

Hiv 1 ◽

Cell Cell

ABSTRACT Cells constituting the placental barrier secrete soluble factors that may participate in controlling human immunodeficiency virus type 1 (HIV-1) transmission from the mother to the fetus. In this study, we asked whether placental soluble factors (PSF) could limit cell-cell contact inducing HIV-1 production that occurs after inoculation of HIV-1-infected peripheral blood mononuclear cells (HIV-1+ PBMCs) onto trophoblast-derived BeWo cells grown as tight and polarized barriers in a two-chamber system. The activity of recombinant chemokines and cytokines expressed by placental tissue and of factors secreted by either early or term placentae of HIV-1-negative women, was analyzed. We identified chemokines (RANTES and MIP-1β) and cytokines (tumor necrosis factor alpha and interleukin-8) that decreased and increased, respectively, viral production in trophoblast barrier cells inoculated with HIV-1+ PBMCs. Unexpectedly, factors secreted by either early or term placentae of HIV-1-negative women enhanced viral production. Nevertheless, the same PSF did not favor infection of trophoblastic barriers with cell-free HIV-1 and strongly reduced viral production in PBMCs infected with cell-free HIV-1. Moreover, PSF contained chemokines (RANTES and MIP-1β) and a cytokine, leukemia inhibitory factor, exhibiting a strong anti-HIV-1 activity in our model of cell-to-cell infection. Together these data suggested that at the maternal interface the global activity of PSF is related to the synergistic action of several soluble factors with a balance in favor of an enhancing activity on the passage of viruses across the trophoblast barrier. This could explain the presence of viral sequences in trophoblasts in all placentae of HIV-1-infected women.

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Inhibition of human immunodeficiency virus type 1 replication by Z-100, an immunomodulator extracted from human-type tubercle bacilli, in macrophages

Journal of General Virology ◽

10.1099/vir.0.80046-0 ◽

2004 ◽

Vol 85 (9) ◽

pp. 2603-2613 ◽

Cited By ~ 7

Author(s):

Yutaka Emori ◽

Tamako Ikeda ◽

Takashi Ohashi ◽

Takao Masuda ◽

Tadashi Kurimoto ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Leukemia Virus ◽

Specific Inhibitor ◽

Human Monocyte ◽

Interleukin 12 ◽

Immunodeficiency Virus ◽

Hiv 1

Z-100 is an arabinomannan extracted from Mycobacterium tuberculosis that has various immunomodulatory activities, such as the induction of interleukin 12, interferon gamma (IFN-γ) and β-chemokines. The effects of Z-100 on human immunodeficiency virus type 1 (HIV-1) replication in human monocyte-derived macrophages (MDMs) are investigated in this paper. In MDMs, Z-100 markedly suppressed the replication of not only macrophage-tropic (M-tropic) HIV-1 strain (HIV-1JR-CSF), but also HIV-1 pseudotypes that possessed amphotropic Moloney murine leukemia virus or vesicular stomatitis virus G envelopes. Z-100 was found to inhibit HIV-1 expression, even when added 24 h after infection. In addition, it substantially inhibited the expression of the pNL43lucΔenv vector (in which the env gene is defective and the nef gene is replaced with the firefly luciferase gene) when this vector was transfected directly into MDMs. These findings suggest that Z-100 inhibits virus replication, mainly at HIV-1 transcription. However, Z-100 also downregulated expression of the cell surface receptors CD4 and CCR5 in MDMs, suggesting some inhibitory effect on HIV-1 entry. Further experiments revealed that Z-100 induced IFN-β production in these cells, resulting in induction of the 16-kDa CCAAT/enhancer binding protein (C/EBP) β transcription factor that represses HIV-1 long terminal repeat transcription. These effects were alleviated by SB 203580, a specific inhibitor of p38 mitogen-activated protein kinases (MAPK), indicating that the p38 MAPK signalling pathway was involved in Z-100-induced repression of HIV-1 replication in MDMs. These findings suggest that Z-100 might be a useful immunomodulator for control of HIV-1 infection.

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Proteomic and Biochemical Analysis of Purified Human Immunodeficiency Virus Type 1 Produced from Infected Monocyte-Derived Macrophages

Journal of Virology ◽

10.1128/jvi.01013-06 ◽

2006 ◽

Vol 80 (18) ◽

pp. 9039-9052 ◽

Cited By ~ 303

Author(s):

Elena Chertova ◽

Oleg Chertov ◽

Lori V. Coren ◽

James D. Roser ◽

Charles M. Trubey ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Multivesicular Body ◽

Human Monocyte ◽

Cell Types ◽

Rab Proteins ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infects CD4+ T lymphocytes and monocytes/macrophages, incorporating host proteins in the process of assembly and budding. Analysis of the host cell proteins incorporated into virions can provide insights into viral biology. We characterized proteins in highly purified HIV-1 virions produced from human monocyte-derived macrophages (MDM), within which virus buds predominantly into intracytoplasmic vesicles, in contrast to the plasmalemmal budding of HIV-1 typically seen with infected T cells. Liquid chromatography-linked tandem mass spectrometry of highly purified virions identified many cellular proteins, including 33 previously described proteins in HIV-1 preparations from other cell types. Proteins involved in many different cellular structures and functions were present, including those from the cytoskeleton, adhesion, signaling, intracellular trafficking, chaperone, metabolic, ubiquitin/proteasomal, and immune response systems. We also identified annexins, annexin-binding proteins, Rab proteins, and other proteins involved in membrane organization, vesicular trafficking, and late endosomal function, as well as apolipoprotein E, which participates in cholesterol transport, immunoregulation, and modulation of cell growth and differentiation. Several tetraspanins, markers of the late endosomal compartment, were also identified. MDM-derived HIV contained 26 of 37 proteins previously found in exosomes, consistent with the idea that HIV uses the late endosome/multivesicular body pathway during virion budding from macrophages.

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