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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of studies examining interactions of dendritic cell (DC)-specific ICAM-3 grabbing nonintegrin (DC-SIGN) with viral pathogens have relied on monocytic transfectants as models for primary DCs. Here we show that the presumed "THP-1" monocytic cells used in these studies are instead Raji B cells. Moreover, we demonstrate that true THP-1 cells do not support DC-SIGN-mediated HIV-1 transmission, whereas human B cell lines efficiently enhance this process. These data indicate that there are features common to B cells and DCs that facilitate transmission of HIV-1 and provide new insights toward the mechanism of DC-SIGN-mediated HIV-1 transmission.
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PMID:Raji B cells, misidentified as THP-1 cells, stimulate DC-SIGN-mediated HIV transmission. 1497 30

Hepatitis C virus (HCV) is a major health problem. However, the mechanism of hepatocyte infection is largely unknown. We demonstrate that the dendritic cell (DC)-specific C-type lectin DC-SIGN and its liver-expressed homologue L-SIGN/DC-SIGNR are important receptors for HCV envelope glycoproteins E1 and E2. Mutagenesis analyses demonstrated that both HCV E1 and E2 bind the same binding site on DC-SIGN as the pathogens human immunodeficiency virus type 1 (HIV-1) and mycobacteria, which is distinct from the cellular ligand ICAM-3. HCV virus-like particles are efficiently captured and internalized by DCs through binding of DC-SIGN. Antibodies against DC-SIGN specifically block HCV capture by both immature and mature DCs, demonstrating that DC-SIGN is the major receptor on DCs. Interestingly, internalized HCV virus-like particles were targeted to nonlysosomal compartments within immature DCs, where they are protected from lysosomal degradation in a manner similar to that demonstrated for HIV-1. Lewis X antigen, another ligand of DC-SIGN, was internalized to lysosomes, demonstrating that the internalization pathway of DC-SIGN-captured ligands may depend on the structure of the ligand. Our results suggest that HCV may target DC-SIGN to "hide" within DCs and facilitate viral dissemination. L-SIGN, expressed by THP-1 cells, internalized HCV particles into similar nonlysosomal compartments, suggesting that L-SIGN on liver sinusoidal endothelial cells may capture HCV from blood and transmit it to hepatocytes, the primary target for HCV. We therefore conclude that both DCs and liver sinusoidal endothelial cells may act as reservoirs for HCV and that the C-type lectins DC-SIGN and L-SIGN, as important HCV receptors, may represent a molecular target for clinical intervention in HCV infection.
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PMID:Hepatitis C virus targets DC-SIGN and L-SIGN to escape lysosomal degradation. 1525 4

Progressive immunodeficiency in HIV infection is paralleled by a decrease in IL-12 production, a cytokine crucial for cellular immune function. Here we examine the molecular mechanisms by which HIV infection suppresses IL-12 p40 expression. HIV infection of THP-1 myeloid cells resulted in decreased LPS-induced nuclear factor binding to the NF-kappaB, AP-1, and Sp1 sites of the IL-12 p40 promoter. By site-directed mutagenesis we determined that each of these sites was necessary for transcriptional activation of the IL-12 p40 promoter. Binding of NF-kappaB p50, c-Rel, p65, Sp1, Sp3, c-Fos, and c-Jun proteins to their cognate nuclear factor binding sites was somewhat impaired by HV infection, although a role for other as yet unidentified factors cannot be dismissed. The cellular levels of these transcription factors were unaffected by HIV infection, with the exception of a decrease in expression of NF-kappaB p65, consistent with the observed decrease in its binding to the IL-12 p40 promoter following HIV infection. Analysis of regulation of upstream LPS-induced MAP kinases demonstrated impaired phosphorylation of JNK and p38 MAPK, and suppressed phosphorylation and degradation of IkappaBalpha following HIV infection. These results suggest that alterations in nuclear factor binding to numerous sites in the IL-12 p40 promoter, together may contribute to the suppression in IL-12 p40 transcription previously reported. These effects on nuclear factor binding may be a direct effect of HIV infection on the IL-12 p40 promoter, or may occur indirectly as a consequence of altered MAP kinase activation.
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PMID:Disruption of MAP kinase activation and nuclear factor binding to the IL-12 p40 promoter in HIV-infected myeloid cells. 1527 Aug 50

Regulation of cytokine and chemokine expression in microglia may have implications for CNS inflammatory disorders. In this study we examined the role of the cyclopentenone PG 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) in microglial inflammatory activation in primary cultures of human fetal microglia. 15d-PGJ(2) potently inhibited the expression of microglial cytokines (IL-1, TNF-alpha, and IL-6). We found that 15d-PGJ(2) had differential effects on the expression of two alpha-chemokines; whereas the Glu-Lys-Arg (ELR)(-) chemokine IFN-inducible protein-10/CXCL10 was inhibited, the ELR(+) chemokine IL-8/CXCL8 was not inhibited. These findings were shown in primary human microglia and the human monocytic cells line THP-1 cells, using diverse cell stimuli such as bacterial endotoxin, proinflammatory cytokines (IL-1 and TNF-alpha), IFN-beta, and HIV-1. Furthermore, IL-8/CXCL8 expression was induced by 15d-PGJ(2) alone or in combination with TNF-alpha or HIV-1. Combined results from EMSA, Western blot analysis, and immunocytochemistry showed that 15d-PGJ(2) inhibited NF-kappaB, Stat1, and p38 MAPK activation in microglia. Adenoviral transduction of super-repressor IkappaBalpha, dominant negative MKK6, and dominant negative Ras demonstrated that NF-kappaB and p38 MAPK were involved in LPS-induced IFN-inducible protein 10/CXCL10 production. Interestingly, although LPS-induced IL-8/CXCL8 was dependent on NF-kappaB, the baseline or 15d-PGJ(2)-mediated IL-8/CXCL8 production was NF-kappaB independent. Our results demonstrate that 15d-PGJ(2) has opposing effects on the expression of two alpha-chemokines. These data may have implications for CNS inflammatory diseases.
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PMID:15-deoxy-Delta12,14-prostaglandin J2 inhibits IFN-inducible protein 10/CXC chemokine ligand 10 expression in human microglia: mechanisms and implications. 1532 15

It has been previously demonstrated that platelets (PLTs) can bind and transport HIV-1 infectious virions. Hepatitis C virus (HCV)-HIV-1 co-infection occurs frequently among users of illicit intravenous drugs, thereby increasing the severity of HIV disease and the evolution towards chronic active hepatitis and hepatocellular carcinoma of HCV-related hepatitis. In the present study we investigated whether or not PLTs can carry HCV, and studied the binding mechanisms. Purified PLTs, obtained from healthy donors, HCV negative and HIV negative, were adsorbed with HCV-containing serum and then employed to infect a THP-1 monocytoid cell line. Replication of HCV was observed as shown by positivity for the E2 antigen within THP-1 cells, by indirect immunofluorescence; moreover, HCV-RNA was detected in supernatants of THP-1 cells at day 7 post-incubation with HCV-adsorbed PLTs. The binding of HCV to PLTs seems to involve fibronectin (FN), as already shown in the case of HIV-1. Indeed, treatment with RGD (Gly-Arg-Gly-Asp-Ser), the key oligopeptide of FN binding, inhibits the ability of HCV to be carried by PLTs in infective forms; the same phenomenon occurs with Mabs to FN. Moreover the infection of THP-1 cells seems to increase FN surface expression, as demonstrated by immunofluorescence tests.
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PMID:HCV infective virions can be carried by human platelets. 1538 45

Hepatitis C virus (HCV) is the main cause of hepatocellular carcinoma in industrialized countries. HCV-HIV-1 co-infection occurs frequently among users of illicit intravenous drugs, thereby increasing the severity of HIV disease and the evolution of chronic active hepatitis towards cirrhosis and hepatocellular carcinoma. The present work shows that THP-1 monocytoid cells are susceptible to HCV infection, of strain 1b, and that this strain can induce cellular modifications in this cell line. Infection of HCV was demonstrated by positivity for the E2 antigen within THP-1 cells and by indirect immunofluorescence; moreover, HCV-RNA was detected in supernatants of THP-1 cells from day 7 post-inoculation. Cell shape and membrane surface antigens varied upon viral infection, which is also capable of inducing oxygen radicals. In particular we underline the relevant intracellular accumulation of ferritin that paralleled an increase of cell surface expression of the transferrin receptor. Evaluation of cellular events upon HCV infection in THP-1 cells may represent a useful tool with which to identify alteration in monocytes metabolism and to study therapeutic approaches for such alterations.
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PMID:Effect of HCV infection on THP-1 monocytoid cells. 1551 25

HIV-1 infection is a major cause of worldwide epidemic of tuberculosis. There is increasing clinical evidence that coinfection with M. tuberculosis accelerates progression of AIDS. We found that, in vivo, HIV-1 load and mutation increase in involved lung segments in patients with pulmonary tuberculosis. We also reported that Mycobacterium tuberculosis stimulates HIV-1 replication by enhancing transcription on the 5' LTR in a macrophage cell line, THP-1, in vitro. In contrast, HIV-1 replication is suppressed by M. tuberculosis infection of monocytes derived macrophages (MDM) or differentiated monocytic THP-1 cells. We observed that HIV-1 5' LTR function was repressed in PMA differentiated THP-1 cells after co-infection with M. tuberculosis. Point mutations in C/EBP beta binding domains of the HIV-1 LTR negative regulatory element (NRE) abolished promoter repression. Monocyte-derived macrophages and differentiated THP-1 cells increased expression of the 16kDa inhibitory form of C/EBP after M. tuberculosis co-infection. Bronchoalveolar lavage cells obtained from normal controls and alveolar macrophages from uninflamed lung of tuberculosis patients also expressed the 16kDa inhibitory form of C/EBP. However, alveolar macrophages from lung segments involved with pulmonary tuberculosis had markedly reduced C/EBP expression. These data suggest that 16kDa isoform of C/EBP plays an important role for the control of HIV-1 replication in macrophages. We propose derepression of HIV-1 LTR mediated transcription as one mechanism for enhanced HIV-1 replication observed in pulmonary tuberculosis. Since the cellular immune response in pulmonary tuberculosis requires lymphocyte/macrophage interaction, a model system was developed in which lymphocytes were added to AM. Contact between lymphocytes and AM reduced inhibitory C/EBP beta, activated NF-kappaB and enhanced HIV-1 replication. If contact between lymphocytes and macrophages was prevented, inhibitory C/EBP beta expression was maintained and the HIV-1 long terminal repeat (LTR) was not maximally stimulated although NF-kappaB was activated. Antibodies which cross-linked macrophage expressed B-7, VCAM and CD-40 were used mimic lymphocyte contact. Cross-linking antibodies abolished inhibitory C/EBP beta expression; however, the HIV-1 LTR was not maximally stimulated and NF-kappaB was not activated. Maximal HIV-1 LTR stimulation required both lymphocyte derived soluble factors and cross-linking of macrophage expressed co-stimulatory molecules. These results demonstrate that neither contact nor soluble factor(s) are sufficient to maximally enhance HIV-1 LTR activity in macrophages. Contact between activated lymphocytes and macrophages is necessary to downregulate inhibitory C/EBP beta, thereby derepressing the HIV-1 LTR. Lymphocyte derived soluble factor(s) activate NF-kappaB, further enhancing the HIV-1 LTR.
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PMID:[Molecular pathogenesis in tuberculosis complicated with AIDS]. 1572 91

Pulmonary tuberculosis (TB) has been characterized by inflammation with increased pro- or anti-inflammatory cytokines produced by macrophages. We have reported that IFN produces inhibitory C/EBPbeta and represses transcription of the HIV-1 LTR in macrophages. STAT-1 and type I IFN receptor knockout mice have macrophages that are defective in IFN signaling, yet LPS stimulation induces inhibitory C/EBPbeta, demonstrating that other cytokines can induce this repressor. LPS or Mycobacterium tuberculosis-derived lipoarabinomannan induce the anti-inflammatory cytokine interleukin (IL)-10, which represses the HIV-1 LTR in differentiated THP-1 macrophages by inducing inhibitory C/EBPbeta. In contrast, in undifferentiated THP-1 monocytes, IL-10 did not inhibit HIV-1 replication or induce C/EBPbeta. IL-10 signal transduction uses STAT-3, and macrophages from STAT-3-/- mice fail to produce inhibitory C/EBPbeta after LPS or IL-10 stimulation. Transfection of STAT-3 into THP-1 cells enhances C/EBPbeta promoter activity. THP-1 differentiation also increases STAT-3 protein, but not STAT-3 gene transcription, and induces a translational regulator, CUG-binding protein, that was essential for production of C/EBPbeta. Differentiation induced post-transcriptional regulation is required to produce inhibitory C/EBPbeta in response to IL-10. Only macrophages are able to repress HIV-1 LTR promoter activity and inhibit viral replication in response to IL-10 or type I IFN.
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PMID:Interleukin-10 induces inhibitory C/EBPbeta through STAT-3 and represses HIV-1 transcription in macrophages. 1601 96

With the discovery that changes in the biological properties of HIV-1 correlate with the progression to disease, it became more and more important to develop assays to distinguish between the viral phenotypes. In this chapter, it is described how the biological phenotype of HIV-1 with regard to cellular tropism can be determined on primary monocyte-derived macrophages, established T-cell lines: MT2, SupT1, and H9, and promonocytic cell lines: U937, HL-60, and THP-1.
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PMID:Determination of cell tropism of HIV-1. 1606 85

Interleukin (IL)-18 is a proinflammatory cytokine that plays an important role in both innate and adaptive immune responses against several infectious pathogens. Relatively little is known about its production in HIV-1 infection, and there are controversial data on the influence of IL-18 on HIV-1 replication in vitro. In this study, we investigated the effect of HIV-1 infection, and challenge with recombinant HIV-1 proteins, on IL-18 production by THP-1 cells. This is a monocytoid cell line spontaneously producing IL-18, and consequently is particularly suitable for the study of HIV-1 effects on this type of cytokine regulation. The results reported here demonstrate a significant reduction in IL-18 secretion during HIV-infection. In fact, low levels of IL-18 were released until 120 h from viral challenge (15 +/- 11 pg/mL at 24 h and 17 +/- 13 at 96 h and < 12.5 at 120 h), whereas IL-18 production by uninfected control cells was 193 +/- 104 pg/mL and 214 +/- 114 pg/mL at 24 h and 120 h respectively. At 168 h of incubation, IL-18 production by infected and uninfected cells was found to be 164 +/- 88 pg/mL and 325 +/- 101 pg/mL respectively (p = 0.001). Of the following viral proteins: gp 120, p24 and Nef, only the last one induced decreased IL-18 secretion in the supernatants of THP-1 cells. This effect is more evident with the concentrations of 5 -1.25 microg/mL of Nef protein (p < 0.0001). In conclusion, our data show that HIV-1 and its regulatory protein, Nef, are able to down-regulate the release of IL-18, in vitro. These results confirm that a variety of modulating effects on the immune response, induced by HIV-infection, may facilitate progression of HIV-1 infection.
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PMID:Regulation of interleukin-18 by THP-1 monocytoid cells stimulated with HIV-1 and Nef viral protein. 1626 57


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