Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Visna virus is a pathogenic lentivirus of sheep tat is distantly related to the primate lentiviruses, including human immunodeficiency virus type 1. The visna virus genome encodes a small regulatory protein, Tat, which is necessary for efficient viral replication and enhanced viral transcription. To investigate the mechanism of action of the visna Tat protein and to localize the protein domain(s) responsible for transcriptional activation, chimeric proteins containing visna virus Tat sequences fused to the DNA binding domain of the yeast transactivation factor GAL4 (residues 1 to 147) were made. The GAL4-Tat fusion proteins were transfected into cells and tested for the ability to activate the adenovirus E1b promoter via upstream GAL4 DNA binding sites. Full-length GAL4-Tat fusion proteins were weak transactivators in this system, giving only a two- to fourfold increase in transcription in several cell types, including HeLa and sheep choroid plexus cells. In contrast, fusion of the N-terminal region of the Tat protein to GAL4 revealed a potent activation domain. Amino acids 13 to 38 appeared to be the most critical for activation. No other region of the protein showed any activation in the GAL4 system. This N-terminal region of the visna virus Tat protein has a large number of acidic and hydrophobic residues, suggesting that Tat has an acidic activation domain common to many transcriptional transactivators. Mutations in hydrophobic and bulky aromatic residues dramatically reduced the activity of the chimeric protein. Competition experiments suggest that mechanism of the visna virus Tat activation domain may closely resemble that of the herpesvirus activator VP16 and human immunodeficiency virus Tat, a related lentivirus activator, since both significantly reduce the level of visna virus Tat activation. Finally, a domain between residues 39 and 53 was identified in the Tat protein that, in the GAL4 system, negatively regulates activation by Tat.
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PMID:Visna virus Tat protein: a potent transcription factor with both activator and suppressor domains. 808 55

Visna-maedi virus is a lentivirus closely related to the human immunodeficiency virus type I (HIV-I). During spontaneous infection of sheep by Visna-maedi virus an interstitial lung disease is observed. It is characterized by an alveolitis, peribronchovascular lymphoid nodules, alveolar wall thickening and myomatosis. In order to decipher the pathology of this lentiviral infection we have induced this disease in colostrum-deprived newborn lambs.
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PMID:Early events in the experimental interstitial lung disease induced in sheep by the Visna-maedi virus. 814 89

Visna-maedi virus is a lentivirus which causes inflammatory disorders in sheep, including a chronic interstitial lung disease resembling that observed in human immunodeficiency virus type 1 (HIV 1) infection. In view of our previous demonstration of the production of neutrophil chemotactic activity by alveolar macrophages, and given the lymphocytic and neutrophilic nature of the alveolar cell infiltrate in both naturally and experimentally infected animals, we hypothesized that interleukin-8 (IL8) could be a candidate for at least part of the chemotactic activity we described. In this study, we investigated IL8 mRNA expression following visna-maedi virus infection. Northern analysis of total RNA using an ovine IL8-specific probe demonstrated that the IL8 gene is upregulated in alveolar macrophages as a consequence of in vitro infection and in alveolar cells from experimentally infected animals. Using a semi-quantitative RT-PCR method, we showed that various levels of IL8 mRNA are expressed by alveolar cells from infected animals and that they correlate with the intensity of the lesions. In conclusion, visna-maedi virus is able to induce IL8 mRNA expression in sheep alveolar cells. Results from in vivo infected animals suggest that IL8 could play a role in the early build-up of visna-maedi virus-induced lesions.
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PMID:Visna-maedi virus-induced expression of interleukin-8 gene in sheep alveolar cells following experimental in vitro and in vivo infection. 890 39

Infection of sheep by visna-maedi virus causes an interstitial pneumonitis similar to that associated with human immunodeficiency virus type-1 (HIV-1). Visna-maedi virus infection of alveolar macrophages leads to their activation. In this study we determined whether an imbalance in oxidant-antioxidant activity may be involved in the pathogenesis of the disease. We investigated the spontaneous and phorbol myristate acetate (PMA)-induced release of hydrogen peroxide (H2O2), and the activities of superoxide dismutase and glutathione peroxidase in alveolar macrophages from lambs experimentally-infected with visna-maedi virus, and in ovine alveolar macrophages infected in vitro. Alveolar macrophages from lambs experimentally-infected in vivo exhibited normal spontaneous H2O2 release and had superoxide dismutase and glutathione peroxidase activities similar to those from control animals. In contrast, after in vitro stimulation with PMA the H2O2 production by macrophages from experimentally-infected lambs was significantly increased. Similarly, spontaneous and PMA-induced H2O2 production by in vitro infected macrophages was significantly increased as compared to controls. In conclusion, the increased capacity of alveolar macrophages infected with the human immunodeficiency virus type-1-related visna-maedi virus to release hydrogen peroxide on stimulation suggests an oxidant-antioxidant imbalance, which may contribute to the pathogenesis of the observed chronic interstitial pneumonitis.
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PMID:Oxidant-antioxidant imbalance in the experimental interstitial lung disease induced in sheep by visna-maedi virus. 890 54

Lentiviruses such as Maedi Visna virus (MVV) in sheep, and human immunodeficiency virus (HIV) in man often cause a variety of neurological syndromes in later stages of infection. Neuropathological investigations reveal damage to myelin and astrocytosis in both white and grey matter. MVV infection induces axonal damage with some areas of necrosis while neuronal loss, and synaptic damage have been reported in HIV-1 infection. It is not clear, at present, how this neurodegeneration is mediated but, as these viruses do not directly infect neurons, an indirect neurotoxic action of the viruses is indicated. Previous experiments have shown that the intra-striatal injection in rats of a synthetic peptide derived from the basic region of the MVV transactivating protein Tat causes considerable neurotoxicity 1 week post-operatively. By in vivo stereotaxic injections of the same synthetic peptide, and subsequent immunocytochemical detection of neurons, astrocytes and microglia, we show that this neurotoxicity displays a distinctive and unusual lesion profile and is evident as rapidly as 0.5 h post-operatively. Furthermore, neuroprotection studies suggest that the early effects of the MVV tat peptide may involve glutamate neurotoxicity via the N-methyl-D-aspartate (NMDA) receptors since the application of dizolcipine (MK801) reduces the volume of the lesion seen at 1 h after the injection of neurotoxic peptide, while L-NAME is ineffective. The mechanism of this early neurotoxicity is thus different from the longer term actions already described.
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PMID:Acute in vivo neurotoxicity of peptides from Maedi Visna virus transactivating protein Tat. 1036 85

The concept of slow virus diseases was developed by Sigurdsson in the 1950s in studies of infections of Icelandic sheep, including Visna, a slow (lenti) viral infection of the central nervous system. Human immunodeficiency virus (HIV) belongs to the same lentivirus subfamily of retroviruses and causes significant dysfunction of all levels of the nervous system. Highly active antiretroviral therapy should allow host control of opportunistic infections, producing a clinical state of chronic-treated HIV. However, viral persistence may occur in the sanctuary of the central nervous system. As a consequence, major disabilities in the chronic-treated phase of the HIV epidemic may include cognitive impairment, gait disorders, and various pain syndromes. Policy planning will need to take into account the long-term residential, social, and health care needs of this population.
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PMID:Chronic-treated HIV: a neurologic disease. 1085 1

All lentiviruses contain an open reading frame located shortly upstream or inside of the env gene and encoding a small protein which has been designated Tat. This designation was mainly with respect to the positional analogy with the first exon of the trans-activator protein of the well studied human immunodeficiency virus type 1 (HIV-1). In this work we comparatively studied the trans- activation activity induced by Tat proteins of the small ruminant Maedi Visna virus (MVV) of sheep and Caprine arthritis encephalitis virus (CAEV) of goats on MVV and CAEV LTRs with that induced by the human lentivirus HIV-1 on its own LTR. The HIV-1 LTR alone weakly expresses the reporter GFP gene except when the HIV-1 Tat protein is coexpressed, the GFP expression is increased 60-fold. In similar conditions only minimal trans-activation increasing two- to three-fold the MVV and CAEV LTR activity was found with MVV Tat protein, and no trans-activation activity was detected in any used cell type or with any virus strain when CAEV Tat was tested. These results indicate that the small ruminant lentiviruses (SRLV) differ from the primate lentiviruses in their control of expression from the viral LTRs and put into question the biological role of the encoded protein named "Tat."
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PMID:Lack of trans-activation function for Maedi Visna virus and Caprine arthritis encephalitis virus Tat proteins. 1266 1

Visna/maedi virus (VMV) causes severe encephalitis and a progressive demyelinating disease in sheep. Previous in vitro studies have demonstrated that VMV-infection leads to apoptosis in sheep choroid plexus cells (SCPC) via induction of both intrinsic and extrinsic pathways with subsequent activation of caspases. 3' azido-2',3'-deoxythymidine (AZT) is a potent and selective Human immunodeficiency virus 1 (HIV-1) reverse transcriptase inhibitor, widely used in antiretroviral therapy; however its effects on retrovirus-induced apoptosis are unknown. Using diverse strategies to detect apoptosis, we analysed the broad range effect of AZT treatment on inhibition of VMV-induced apoptosis. First, we found that AZT treatment inhibited the appearance of characteristic apoptotic morphologic changes documented by DAPI staining and oligonucleosomal DNA laddering. Secondly, AZT treatment inhibited caspase cascade and resulted in (i) diminished caspase-3, -8 and -9 activities and (ii) no fluorescein isothiocynate-[VAD]-fluoromethylketone (FITC-VAD-FMK) in situ labelling in VMV-infected cells treated with AZT. Finally, immunocytochemistry indicated that VMV-infection of SCPC induced the subsequent release of apoptosis inducing factor (AIF), whereas AZT treatment inhibited AIF leakage. Consequently, the anti-apoptotic effects of AZT are not restricted, since AZT treatment blocks all the apoptotic pathways induced during VMV-infection.
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PMID:AZT inhibits Visna/maedi virus-induced apoptosis. 1499 45

Lentiviral-based vectors have been widely used lately in preclinical studies and for the in vitro genetic manipulation of embryonic and adult stem cells. They allow for the transduction of nondividing cells and for stable gene expression. On these grounds, lentiviral vectors look promising for eventual applications for the gene-based treatment of neurological disorders, cardiopathies and inherited or acquired genetic diseases. The best developed and characterized lentiviral vector system is based on the human immunodeficiency virus type 1 (HIV-1). However, safety concerns preclude any possible application of HIV-1-derived vectors in clinical trials. For this reason, gene therapists are currently improving the design of other lentiviral vectors, such as feline immunodeficiency virus, equine anemia infectious virus and Visna virus. These lentiviruses are not pathogenic in humans and are only distantly related to primate Retroviridae. This review summarizes the achievements in improving the design of lentiviral vector systems that are not based on HIV-1.
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PMID:Current development of lentiviral-mediated gene transfer. 1588 21


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