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

We have described the isolation of chemically induced CEM subclones that express CD4 receptors and bind soluble gp120, yet show a markedly reduced susceptibility to infection with HIV-1. Two subclones were found to have an abnormal response to the protein kinase C (PKC) activator PMA. PMA treatment induced CD3 and CD25 (IL-2R) receptors on the parental line and on other ethyl-methanesulfonate-derived subclones, but not on these two mutants. Direct assays of PKC activity were conducted. Total cellular PKC enzymatic activity was found to be normal in these subclones. PMA-induced CD4 down-modulation occurred normally. In addition, activation of c-raf kinase was normal. Since HIV-1 long terminal repeat contains two functional nuclear factor kB (NF-kB) regulatory elements, we studied the ability of PMA to induce NF-kB binding activity by different assays. Chloramphenicol acetyl transferase (CAT) assays using the HIV-1 (-139)long terminal repeat-CAT construct showed no PMA induction of CAT activity in these subclones (unlike the parental line and other subclones). Okadaic acid, an inhibitor of phosphatases 1 and 2A, did not overcome the defect in these subclones. Gel retardation assays, using a 32P-probe containing the HIV-1 NF-kB probe and nuclear extracts from PMA-treated cells, showed significantly reduced induction of nuclear NF-kB binding proteins in these two subclones compared with wild type CEM and a control subclone. Deoxycholate treatment of cytoplasmic extracts from these subclones released much reduced NF-kB binding proteins from their cytoplasmic pools. Thus, reduced levels of PKC-induced nuclear NF-kB activity in two T cell subclones did not affect their normal cell growth, but correlated with a pronounced reduction in their susceptibility to HIV-1 infection.
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PMID:Reduced susceptibility to HIV-1 infection of ethyl-methanesulfonate-treated CEM subclones correlates with a blockade in their protein kinase C signaling pathway. 135 Oct 90

Vitamin A and other retinoids have profound effects on macrophage differentiation and function. Such effects could alter interactions between HIV and tissue macrophages, a principal target cell and reservoir for virus during HIV disease. Indeed, retinoids are used to treat various symptoms associated with HIV infection. We show that levels of virus replication in monocytes cultured 7 days before and continuously after HIV infection in 1 to 10 microM retinoic acid were 10- to 20-fold greater than those of control cells. No direct toxicity (detachment from substrate or cell death) was evident in infected or control monocytes treated with less than or equal to 10 microM retinoic acid. Maximum effects of retinoic acid (50% maximum effect was at 0.8 +/- 0.1 microM) required 5 to 7 days treatment before infection and persisted without additional treatment through more than 4 wk. RT activity in cultures of retinoic acid-treated monocytes reached maximum levels much earlier than those of control cultures, but the minimum tissue culture infectious doses for retinoic acid-treated and untreated monocytes were comparable. Retinoic acid treatment did not affect susceptibility of monocytes to HIV infection. Further, the frequency of infected cells in retinoic acid-treated and control cultures were also comparable: about 20% of cells in each culture expressed HIV proteins or RNA 2 wk after infection. In contrast, levels of HIV-specific RNA and DNA were 3- to 5-fold higher in the retinoic acid-treated over control monocytes 1 wk after infection. That retinoic acid increased levels of HIV gene expression in monocyte cultures without affecting the number of infected cells per culture suggested a transcriptional mechanism for the effect. This was confirmed in the U937 myeloid cell line transfected with HIV LTR linked to a chloramphenicol acetyl transferase reporter gene. Chloramphenicol acetyl transferase activity in lysates of retinoic acid-treated cells were 20-fold higher than that of control cells. These data show that retinoic acid significantly increased HIV replication in monocytes through mechanisms related to cell differentiation and to a direct transcriptional effect on viral gene expression.
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PMID:Enhanced HIV-1 replication in retinoid-treated monocytes. Retinoid effects mediated through mechanisms related to cell differentiation and to a direct transcriptional action on viral gene expression. 156 Feb 8

Transcriptional regulation of the proviral form of the human immunodeficiency virus type 1 (HIV-1) is exerted by its 5' long terminal repeat (LTR), which contains recognition sites for several cell factors. By gel retardation and DNase I footprinting experiments we have identified a binding site for a human nuclear protein between nucleotides -152 to -174 upstream of transcription start site, in a region previously recognized as a negative regulator of transcription (negative regulatory element, NRE). The recognized sequence contains the dyad symmetry element CACGTG, which represents a binding motif, very conserved through evolution, present in a putative human DNA replication origin (pB48), in the upstream element of the major late promoter (MLP-UE) of adenovirus, and, as transcriptional element, upstream of many eukaryotic genes. Common binding activities exist in human nuclear extracts for pB48, MLP-UE and the HIV-1 LTR; at least three protein species recognize the LTR sequence, of 44 (corresponding to transcription factor USF/MLTF), 70, and 110 kDa, respectively. Chloramphenicol acetyltransferase assays suggest that the USF/MLTF binding site located in the HIV-1 LTR acts as a negative regulator of transcription, and that it contributes to the overall negative function exerted by the NRE. An oligonucleotide corresponding to another characterized human USF/MLTF binding site can functionally replace part of the activity of the NRE. This negative function is exerted both in presence or absence of tat transactivation, in different cell lines, and after PMA stimulation.
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PMID:A human binding site for transcription factor USF/MLTF mimics the negative regulatory element of human immunodeficiency virus type 1. 172 95

Inpatient and community-based care can be complementary in relation to the management of HIV disease. Medical records from 200 inpatients of Chikankata Hospital near Lusaka, Zambia and 200 home based patients were examined and compared for the common symptoms of presentation of HIV disease, associated opportunistic infections, and treatment protocols. Drug costs of both groups were also compared. The most common respiratory symptoms in the 2 groups are cough, chest pains, weight loss, and hemoptysis. Treatment employed for these symptoms were cortimoxazole, penicillin V, erthromycin, and tetracycline. Acetyl saliclic acid and paracetamol were used for pain relief in both groups. Gastointestinal system symptoms for both groups were diarrhea, weight loss, abdominal pain, and vomiting. Cotrimoxazole and metronidazole were used in treating diarrhea. Additional treatment protocol for the 2 patient samples included oral rehydration therapy for dehydration, antacid or bismuth subsalicylate for diarrhea and enteritis, and mycostatin for oral candidiasis. Central nervous system symptomatology included headache, dementia, neckace, and lethargy. Chloramphenicol was employed in treating bacterial meningitis. Diazepam and chlorpromazine were effective for restless patients. Genito-urinary system symptomatology for the 2 groups included dysuria, genital ulcers, hematuria, viral warts, and buboes. Antibodies were used for sexually transmitted diseases and infections. Skin symptomatology included rash and dermatitis, herpes zoster, abscess, kaposi's sarcoma, ulcers, furunculosis, and discharging anal sinus. In treating these symptoms, hospital based care and home based care were similar. Overall, it was found that hospital treatment protocols were detailed, expensive, and time consuming. Furthermore, hospital treatment for HIV positive patients is more expensive than HIV negative patients; hospital costs for 50 HIV negative patients totaled US$415.94 compared to US$1204.98 HIV positive/PTB negative patients and US$1705.62 for HIV positive/PTB positive patients. Drug cost/patient admission is increased by 469% if HIV positive. (author's modified).
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PMID:Clinical care as part of integrated AIDS management in a Zambian rural community. 248 94

The enhancer element of the human immunodeficiency virus type I (HIV-I) long terminal repeat (LTR) contains two copies of nearly identical sequences AGGGACTTTCC (3G sequence) and GGGGACTTTCC (4G sequence) that are important in transcriptional regulation. A single copy of the 4G sequence is found in the NF-kappa B site of the immunoglobulin kappa-chain enhancer. Only the 4G motif in the HIV enhancer is bound by cellular proteins in extracts prepared from unstimulated HeLa cells, whereas the 3G and 4G motifs are bound by factors in extracts prepared from HeLa cells treated with phorbol esters [phorbol 12-myristate 13-acetate (PMA)] and lymphoid cells. To determine if this change in binding to the HIV enhancer was due to phosphorylation of a cellular protein, partially purified PMA-treated HeLa nuclear extracts were digested with calf intestinal phosphatase. Phosphatase digestion of nuclear extracts from PMA-treated HeLa cells markedly decreased factor binding to the HIV enhancer. Accordingly, phosphorylation of the DNA binding protein itself, or an inhibitor protein present in the partially purified extract, must mediate binding to the recognition sequence. Binding studies confirmed that each of the enhancer sequences was capable of binding factors independent of the activity of the other site and that the HIV enhancer was occupied by only one factor at any one time. Chloramphenicol acetyltransferase assays using mutants in either one or both HIV enhancer repeats revealed that each site was capable of functioning as a tat-inducible enhancer element in PMA-treated HeLa cells. These results suggest that the 3G and 4G motifs in the HIV enhancer function independently and that duplication in the HIV enhancer augments activity by a mechanism distinct from cooperative binding of NF-kappa B.
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PMID:Repeated B motifs in the human immunodeficiency virus type I long terminal repeat enhancer region do not exhibit cooperative factor binding. 320 Aug 27

Monoclonal antibodies (MAb) directed against the immunoglobulin complementary determining region 3 (CDR3)-like region of the CD4 molecule inhibit human immunodeficiency virus type 1 (HIV-1) transcription. We report here data showing that the cytoplasmic tail of CD4 is required for such inhibition to be achieved. To this aim, we studied the effect of MAb 13B8-2 treatment on (i) HIV-1 production in A2.01 cells, which express different forms of the CD4 gene, (ii) Tat-induced HIV-1 promoter activation, and (iii) mitogen-activated protein kinase (MAPK) activation, which is induced in CD4-positive cells by HIV-1 cross-linking of CD4. Inhibition of HIV production by 13B8-2 MAb treatment was consistently observed in cells expressing wild-type CD4 and cells expressing a hybrid CD4-CD8 molecule (amino acids 1 to 177 of CD4 fused to the hinge, transmembrane, and cytoplasmic domains of CD8). However, no delay in HIV-1 production was observed in cells expressing a truncated CD4 which lacks the cytoplasmic domain (CD4.401). Chloramphenicol acetyltransferase assays demonstrated that Tat-dependent activation of the HIV-1 long terminal repeat promoter was inhibited by MAb 13B8-2 in A2.01/CD4 and A2.01/CD4-CD8 but not in A2.01/CD4.401 cells. Finally, we found that MAb 13B8-2 treatment inhibited the activation of MAPK induced in A2.01/CD4 and A2.01/CD4-CD8 following cross-linking of CD4 by HIV-1.
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PMID:The cytoplasmic tail of CD4 is required for inhibition of human immunodeficiency virus type 1 replication by antibodies that bind to the immunoglobulin CDR3-like region in domain 1 of CD4. 747 7

Between 1982 and 1986 in western Zaire, a pediatrician collected data on 206 children under 5 years old presenting at the Institute Medical Evangelique, a 400-bed mission hospital (60 pediatric beds), in Kimpese with persisting fever despite chloroquine therapy for falciparum malaria, a negative or scanty positive thick film for malaria, and no clear localizing signs of infections. The pediatrician suspected that these cases had an extraintestinal Salmonella infection and took blood, synovial fluid, and/or cerebrospinal fluid samples for diagnostic analyses. Salmonella serotypes other than Salmonella typhi (non-S. typhi) were responsible for most bacteremia cases (83%). The clinical features of non-S. typhi and S. typhi infections were basically the same. The case fatality rate for non-S. typhi and S. typhi an S. typhi infections were 22.7% and 29.4%, respectively. Infants under 6 months old had a significantly higher case fatality rate than older children (relative risk [RR] = 1.7; p .0005; e.g., 66% and 100% for infants under 3 months old). Meningitis was significantly associated with increased mortality, regardless of age (RR = 4.68). Jaundice was the only clinical sign significantly linked to increased mortality (RR = 2.35), especially among children who had S. typhi infection (80%). Mortality occurred significantly more often when children fell ill with Salmonella bacteremia in the late rainy season, coinciding with the peak of malnutrition, than in the dry season (RR = 2.62). Chloramphenicol-resistant non-S. typhi isolated were significantly associated with increased mortality (RR = 3.19). Hemoglobin levels below 6 g (i.e. severe anemia) has a strong link to increased mortality (RR = 1.77). Salmonella bacteremia will become more difficult to treat as antibiotic resistance and the prevalence of HIV infection increases in African countries.
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PMID:Salmonella bacteraemia among young children at a rural hospital in western Zaire. 768 45

Asymptomatic syphilis eventually manifesting with symptoms of the secondary disease was observed in a male with HIV-infection. Large focuses of alopecia reported in this male are suggested as a clinical marker of HIV-infection. A defective antibody response to T. pallidum in HIV-infection has been confirmed. Levomycetin (0.5 g 4 times a day in 5-20-day courses at two-week intervals) proved highly effective as compared to penicillin, erythromycin and tetracycline administration due to poor tolerance of the above antibiotics.
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PMID:[An unusual variant of secondary recurrent syphilis in an HIV-infected patient]. 790 39

CD8+ cells from HIV-infected individuals inhibit HIV replication in cultured CD4+ cells by a nonlytic, non-MHC-restricted mechanism. The activity appears to be mediated in part by a soluble antiviral factor (CAF) secreted by the CD8+ cells. In an attempt to identify this factor a large panel of recombinant cytokines was examined for their effect on HIV replication in CD4+ cells. In addition to interferon-alpha and -beta, TNF alpha, TGF beta, and IL-8 reduced virus replication in a dose-dependent fashion. In some cases, the effect of the cytokine was also dependent on the HIV infection assay used to measure it. Antibodies against the inhibitory cytokines, as well as antibodies against TNF beta, IFN-alpha, IFN-beta, IL-4, and IL-6 did not inactivate the antiviral effect of CAF. The data suggest that CAF does not have identity with known antiviral cytokines and therefore CAF may be a novel antiviral factor.
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PMID:Effect of cytokines on HIV replication in CD4+ lymphocytes: lack of identity with the CD8+ cell antiviral factor. 790 3

Tumor necrosis factor alpha (TNF-alpha) and 12-0-tetradecanoyl phorbol-13-acetate (TPA) activate human immunodeficiency virus type 1 (HIV-1) in U1 cells that are latently infected with HIV-1 to produce viral particles. Pertussis toxin, which inactivates several members of the G protein family of signaling components, including Gi, Go, and transducin, was found to inhibit either TPA or TNF-alpha induction of HIV-1 in U1 cells at the concentration of 1-10 ng/ml. Chloramphenicol acetyl transferase (CAT) assay revealed that pertussis toxin could inhibit HIV-1 gene expression. B-oligomer, the mitogenic and non-ADP-ribosylating component of pertussis toxin, did not show any effect on HIV-1 replication alone or in combination with TNF in the same concentration range. It was of particular interest to note that a single protein (Gi) with a molecular weight of 40 kDa was dose-dependently ADP-ribosylated after treatment with pertussis toxin in U1 cells. The degree of ADP ribosylation of Gi corresponded well to that of inhibition of HIV-1 upon treatment with pertussis toxin. These results strongly support the contention that TPA and TNF-alpha induction of HIV-1 is mediated by a Gi-like receptor-effector coupling protein in the membrane of U1 cells. On the basis of these findings, we propose a model for signal transduction of HIV-1 expression through c-kinase-dependent (TPA) and c-kinase-independent (TNF-alpha) pathways in the U1 cell to determine the point at which Gi-like protein is involved.
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PMID:Pertussis toxin inhibits induction of human immunodeficiency virus type 1 in infected monocytes. 805 61


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