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

The recent resurgence of TB together with the ongoing HIV epidemic has resulted in a larger number of infectious TB patients being admitted to US health care facilities. These patients have become a source for both nosocomial (patient-to-patient) and occupational (patient-to-health care worker) M. tuberculosis transmission. Infectious MDR-TB patients serve as even greater potential infectious sources because they often remain AFB smear and culture positive for months to years. The keys to the prevention of nosocomial and occupational transmission of M. tuberculosis is conducting a risk assessment for each area of the facility and instituting appropriate control measures, having a high index of suspicion by clinicians for infectious TB in those who present with consistent signs and symptoms, rapid triage of such patients to isolation areas and their appropriate clinical work-up, and the institution of effective antituberculous therapy. Infection control personnel should ensure that infectious TB patients are isolated in appropriate isolation rooms (i.e., negative pressure, greater than or equal to 6 ACH, and direct external exhaust of the room air). Health care workers with infectious TB patient contact should be instructed in the epidemiology of M. tuberculosis transmission, the role of respirators in protecting the health care worker from airborne inoculation, and the importance of periodic health care worker TST. The nosocomial TB outbreaks in the 1980s and 1990s document that M. tuberculosis can be transmitted to both patients and health care workers in US health care facilities when appropriate infection control measures are not fully implemented. Follow-up studies at some of these institutions, however, document that when infection control measures similar to the 1990 or 1994 CDC TB Guidelines are fully implemented, M. tuberculosis transmission to both patients and health care workers can be reduced or eliminated. Protection of both patients and health care workers from M. tuberculosis infection is dependent on an understanding and full implementation of the 1994 CDC TB Guidelines.
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PMID:Prevention of nosocomial transmission of Mycobacterium tuberculosis. 918 53

Monocytes/macrophages have been known to play an important role in the initiation and propagation of human immunodeficiency virus 1 (HIV-1) infection. To analyze the function of these cells during the clinical asymptomatic period of infection, we examined the effect of murine peritoneal macrophages and human peripheral blood macrophages on two cell lines latently infected with HIV-1, a promonocytic cell line, U1, and a T-cell line, ACH-2. Monokines of the murine peritoneal macrophages induced significant viral expression in U1, but not in ACH-2 cells. Experiments employing transient transfection of U937 and CEM cells with HIV long terminal repeat (LTR)-chloramphenicol acetyl transferase (CAT) plasmids indicated that the effect of these monokines was due to specific activation of the HIV LTR. In contrast, supernatants of human macrophages induced viral expression in both ACH-2 and U1 cells. These results suggest that several monokines are active in regulating the transition from the clinical asymptomatic period of HIV infection to progression to acquired immunodeficiency syndrome (AIDS).
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PMID:Contribution to the regulation of virus replication in cells latently infected with human immunodeficiency virus 1. 919 10

Because of an inherent dependence on host cell second and third messenger signaling pathways for activation of HIV-1 expression, a potential exists for a relationship between the induction of latent HIV-1 and cell-cycle-related events. To investigate this potential relationship, cellular models of latent HIV-1 infection (OM-10.1 promyelocytes, ACH-2 T-lymphocytes, and U1 promonocytes) were chemically treated or gamma-irradiated to synchronize cultures at each cell cycle stage and then examined for constitutive and TNF-alpha-induced HIV-1 expression. Cell cycle synchronization alone had no effect on HIV-1 expression in OM-10.1 and U1 cultures; whereas enhanced constitutive HIV-1 expression was observed in ACH-2 cultures at G2 + M. A 2 hour TNF-alpha treatment of all synchronized OM-10.1 cultures activated HIV-1 expression to a similar extent as unsynchronized cultures. In contrast, the extent of TNF-alpha-induced HIV-1 expression in ACH-2 S and G2 + M cultures and in the U1 G0/G1 culture was greater than that in unsynchronized control cultures. However, no delay in the initial response was observed. Thus, the influence of cell cycle on constitutive and induced HIV-1 expression varied in each cellular model and, therefore, may further relate to the different molecular mechanisms maintaining viral latency.
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PMID:Influence of cell cycle on HIV-1 expression differs among various models of chronic infection. 922

Eleven German laboratories and one Swiss laboratory initiated a quality assessment study to evaluate the specificity and sensitivity of their polymerase chain reaction (PCR) for detection of HIV-1 DNA. Following its own PCR protocols, each laboratory tested a panel of ten coded samples consisting of cell pellets containing 0, 0.1, 1, 10, 10(2), 10(3) and 10(4) ACH-2 cells per 1.5 x 10(5) uninfected peripheral blood mononuclear cells. Of the twelve participating laboratories, three reported correct results for the dilution series as well as for uninfected specimens. One or more classification errors were recorded for 12% of the samples for which the diagnosis was expected to be positive or negative. Samples containing 10 copies of the target template were correctly reported by eleven of the twelve participants. The average sensitivity was 97%. The results of the study revealed no significant differences between the Amplicor kit and in-house procedures. Most of the classification errors occurred in specimens from HIV-negative samples. Out of 36 negative samples, 5 were reported false positive, showing that contamination remains a problem for some laboratories, regardless of the PCR test performed. Careful laboratory techniques and internal as well as external quality control procedures will help avoiding carryover contamination.
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PMID:A multicentre quality assessment study to monitor the performance of HIV-1 PCR. 927 17

The role of the N-myristoylation of the human immunodeficiency virus type 1 (HIV-1) gag protein in ACH-2 cells was studied. The infectivity of HIV-1 from the cells stimulated with phorbol 12-myristate 13-acetate (PMA) was suppressed by pretreatment with N-myristoyl glycinal diethylacetal (N-Myr-GOA), a potent N-myristoylation inhibitor, and the blockage of myristoylation resulted in accumulation of immature gag precursors. The viral particles which budded from the non-N-Myr-GOA-treated ACH-2 cells stimulated with PMA exhibited a typical viral phenotype, whereas those which budded from the N-Myr-GOA-treated ACH-2 cells stimulated with PMA were twisted, as observed electron microscopically. In electron microscopic analyses with gold-labeled monoclonal antibodies to gag and env, gag and env were detected adjacent to each other in the PMA-stimulated ACH-2, but no env was detected in the cells treated with N-Myr-GOA. Taken together, the results suggest that the myristoylation of HIV-1 gag seems to be responsible for both maturation of gag and acquisition of HIV-1 infectivity.
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PMID:Blockage of N-myristoylation of HIV-1 gag induces the production of impotent progeny virus. 929 93

The HIV-1 long terminal repeat (LTR) introduced into the macrophage cell line THP-1 and the T lymphocyte cell line Jurkat in association with the luciferase reporter gene is activated by the polar, aprotic solvents dimethylsulfoxide (DMSO), dimethylacetamide (DMAC), and dimethylformamide (DMF). These solvents also greatly potentiated the activation of the LTR in THP-1 cells by phorbol myristate acetate (PMA), tumor necrosis factor alpha (TNF-alpha), H202, and a Staphylococcus epidermidis product. Lipopolysaccharide (LPS) and lipoteichoic acid (LTA) at 1 microg/ml had no effect on the LTR in THP-1 cells unless the solvents were added. The aprotic solvents also greatly potentiated the activation of the LTR in Jurkat cells by PMA, TNF-alpha, and H202, whereas LPS, LTA, or the S. epidermidis product had no effect in the presence or absence of the solvents. DMSO, DMAC, and DMF also increased the production of intact virions by latently HIV-1-infected ACH-2, J1.1, U1, and OM10.1 cells under some experimental conditions. The use of the polar aprotic solvents DMSO, DMAC, and DMF, by amplification, may allow the better detection of a weak activator of the LTR and facilitate studies of the mechanism of activation.
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PMID:Activation of the HIV type 1 long terminal repeat and viral replication by dimethylsulfoxide and related solvents. 931 Feb 89

Transition from latency to active replication is a crucial stage for the process of human immunodeficiency virus type 1 (HIV-1) infection and life cycle. HIV-1 replication in latently infected cells can be strongly induced by the cytokine tumor necrosis factor alpha (TNF-alpha) and the proliferation-arresting chemical sodium butyrate (NaB). We have investigated the ability of the drug 9-nitrocamptothecin (9NC), a potent cellular topoisomerase I (topo I) inhibitor currently in clinical trials in cancer patients, to regulate HIV-1 replication in latently infected lymphocytic ACH-2 cells on reactivation with either TNF-alpha or NaB. Treatment of ACH-2 cells with 9NC alone resulted in increased levels of viral transcripts, while there was a slight reduction or no change in the levels of host cell transcripts. However, pretreatment of ACH-2 cells with 9NC inhibited TNF-alpha-induced extracellular HIV-1 p24 levels up to approximately 95% and nearly 80% of the cell-associated viral RNAs. The quantitative decrease in viral products was concomitant with a decrease in cellular gene expression and induction of apoptosis in the host cells. 9NC blocked the infected cells at the boundary of the S and G2 phases, resulting in an accelerated apoptosis that was further enhanced with TNF-alpha treatment. Similar results were observed following concurrent exposure to TNF-alpha and 9NC, but 9NC failed to inhibit upregulation of HIV-1 mRNA in ACH-2 cells exposed to TNF-alpha before 9NC treatment. Further, 9NC had no inhibitory effect on NaB-induced apoptosis and upregulation of HIV-1 mRNA expression regardless of whether 9NC and NaB were used concurrently or in various treatment sequences. In uninfected lymphocytic CEM cells derived from a common parental cell line, a slight downregulation of cellular gene expression was detected along with low-level apoptosis. These results demonstrate that 9NC impairs TNF-alpha-induced, but not NaB-induced, HIV-1 activation, and suggest a means of inhibiting active HIV-1 viremia arising as a result of elevated TNF-alpha levels.
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PMID:9-Nitrocamptothecin inhibits tumor recrosis factor-mediated activation of human immunodeficiency virus type 1 and enhances apoptosis in a latently infected T cell clone. 945 50

Determinations of plasma HIV viral RNA copy numbers help to define the kinetics of HIV-1 infection in vivo and to monitor antiretroviral therapy. However, questions remain regarding the identity of various infected cell types contributing to this free virus pool and to the in vivo lifecycle of HIV during disease progression. Characterization of a novel fluorescence in situ hybridization (FISH) assay employing a pool of labeled oligonucleotide probes directed against HIV RNA was done followed by coupling of the FISH assay with simultaneous surface immunophenotyping to address these questions. In vitro characterizations of this assay using tumor necrosis factor-alpha stimulated and unstimulated ACH-2 cells demonstrated the ability to detect < 5% HIV RNA positive cells with a sensitivity of < 30 RNA copies per cell. Peripheral blood mononuclear cells from 39 HIV-seropositive patients on no, single, combination, or triple drug therapy and 8 HIV-seronegative patients were examined. The majority of HIV-positive patients (24/39) harbored monocytes positive for HIV RNA and a significantly higher fraction of patients with high plasma viral load carried positive monocytes (13/16) than did patients in the low plasma viral load group (11/23). These results demonstrate the effectiveness of a novel FISH assay for identifying and monitoring HIV-infected cell populations in the peripheral blood of HIV-positive patients. In addition, monocytes are a major source of cellular HIV virus in the peripheral blood of HIV patients, even with progression of disease.
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PMID:Detection of HIV-RNA-positive monocytes in peripheral blood of HIV-positive patients by simultaneous flow cytometric analysis of intracellular HIV RNA and cellular immunophenotype. 955 2

The HIV-1 protein Rev, critical for translation of incompletely spliced retroviral mRNAs encoding capsid elements, requires a host cell protein termed "eukaryotic initiation factor 5A" (eIF-5A). This is the only protein containing hypusine, a lysine-derived hydroxylated residue that determines its proposed bioactivity, the translation of a subset of cellular mRNAs controlling G1-to-S transit of the cell cycle. We postulated that inhibiting the hypusine-forming deoxyhypusyl hydroxylase (DOHH) should, by depleting eukaryotic initiation factor 5A, compromise Rev function and thus reduce HIV-1 multiplication. We now report that the alpha-hydroxypyridones, specifically mimosine, a natural product, and deferiprone, an experimental drug, inhibited deoxyhypusyl hydroxylase in T-lymphocytic and promonocytic cell lines and, in a concentration-dependent manner, suppressed replication of HIV-1. However, the alpha-hydroxypyridones did not affect the formation of unspliced or multiply spliced HIV-1 transcripts. Rather, these agents caused Rev-dependent incompletely spliced HIV-1 mRNA such as gag, but not cellular "housekeeping" mRNAs, to disappear from polysomes. Consequently, alpha-hydroxypyridone-mediated depletion of eIF-5A decreased biosynthesis of structural HIV-1 protein encoded by gag, measured as p24, whereas the induced formation of cellular protein like tumor necrosis factor alpha remained unaffected. By interfering with the translation of incompletely spliced retroviral mRNAs, these compounds restrict HIV-1 to the early, nongenerative phase of its reproductive cycle. In the inducibly HIV-1 expressing T-cell line ACH-2, the deoxyhypusyl hydroxylase inhibitors triggered extensive apoptosis, particularly of cells that actively produce HIV-1. Selective suppression of retroviral protein biosynthesis and preferential apoptosis of retrovirally infected cells by alpha-hydroxypyridones point to a novel mode of antiretroviral action.
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PMID:Antiretroviral effects of deoxyhypusyl hydroxylase inhibitors: a hypusine-dependent host cell mechanism for replication of human immunodeficiency virus type 1 (HIV-1). 971 99

Cepharanthine is a biscoclaurine alkaloid isolated from Stephania cepharantha Hayata and has been shown to have antiinflammatory, antiallergic, and immunomodulatory activities in vivo. As several inflammatory cytokines and oxidative stresses are involved in the pathogenesis of HIV-1 infection, we investigated the inhibitory effects of cepharanthine on tumor necrosis factor alpha (TNF-alpha)- and phorbol 12-myristate 13-acetate (PMA)-induced HIV-1 replication in chronically infected cell lines. Two chronically HIV-1-infected cell lines, U1 (monocytic) and ACH-2 (T lymphocytic), were stimulated with TNF-alpha or PMA and cultured in the presence of various concentrations of the compound. HIV-1 replication was determined by p24 antigen level. The inhibitory effects of cepharanthine on HIV-1 long terminal repeat (LTR)-driven gene expression and nuclear factor kappaB (NF-kappaB) activation were also examined. Cepharanthine dose dependently inhibited HIV-1 replication in TNF-alpha- and PMA-stimulated U1 cells but not in ACH-2 cells. Its 50% effective and cytotoxic concentrations were 0.016 and 2.2 microg/ml in PMA-stimulated U1 cells, respectively. Cepharanthine was found to suppress HIV-1 LTR-driven gene expression through the inhibition of NF-kappaB activation. These results indicate that cepharanthine is a highly potent inhibitor of HIV-1 replication in a chronically infected monocytic cell line. Since biscoclaurine alkaloids, containing cepharanthine as a major component, are widely used for the treatment of patients with various inflammatory diseases in Japan, cepharanthine should be further pursued for its chemotherapeutic potential in HIV-1-infected patients.
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PMID:Potent inhibition of HIV type 1 replication by an antiinflammatory alkaloid, cepharanthine, in chronically infected monocytic cells. 976 7


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