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)

The CD4 cell surface antigen is of interest as a marker of T lymphocytes that recognize foreign antigens in the context of MHC Class II antigen, as a receptor for the human immunodeficiency virus (HIV) and as a member of the immunoglobulin superfamily (IgSF) with four Ig-like domains present in the extracellular domain. In order to produce large amounts of soluble CD4 for x-ray crystallography and other molecular studies, a recently developed expression system based on selection via glutamine synthetase was used. Expression was attempted for rat CD4 corresponding to the full extracellular sequence (sCD4; domains 1-4), the NH2-terminal half (domains 1 and 2) and the first domain alone. Stable transfected Chinese hamster ovary cell lines were obtained that expressed sCD4 and sCD4 (half) at typical maximal levels in spent tissue culture supernatant of greater than 80 and 25 mg/liter, respectively. Domain 1 alone was not expressed and introduction of a N-linked glycosylation site did not facilitate expression. The role of glycosylation in the expression of sCD4 was investigated by mutagenesis of the constructs to remove each of the two N-linked glycosylation sites in turn and both together. All three forms were expressed at 60-120 mg/liter. The sCD4 (half) was not expressed after deletion of its N-linked site. The disulfide bonds of sCD4 were determined to be within domains 1, 2, and 4 and isolation of glycopeptides showed that both N-linked sites were glycosylated. Analysis of the hydrodynamic properties of sCD4 suggested that the molecule adopted an extended conformation in solution rather than folding to form a compact structure like an Fab. The possibility of dimerisation of CD4 was investigated but sCD4 dimers were not seen at an affinity cut-off of about 4 x 10(5) M-1.
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PMID:High level expression in Chinese hamster ovary cells of soluble forms of CD4 T lymphocyte glycoprotein including glycosylation variants. 211 54

Central nervous system disorders are still a common complication of human immunodeficiency virus (HIV) infection and can lead to dementia and death. They are mostly the consequences of an inflammatory macrophagic activation and relate to glutamate-mediated excitotoxicity. However, recent studies also suggest neuroprotective aspects of macrophage activation through the expression of glutamate transporters and glutamine synthetase. We thus aimed to study whether HIV infection or activation of macrophages could modulate glutamate metabolism in these cells. We assessed the effect of HIV infection on glutamate transporter expression as well as on glutamate uptake by macrophages and showed that glutamate transport was partially decreased in the course of virus replication, whereas excitatory amino acid transporter-2 (EAAT-2) gene expression was dramatically increased. The consequences of HIV infection on glutamine synthetase were also measured and for the first time we show the functional expression of this key enzyme in macrophages. This expression was repressed during virus production. We then quantified EAAT-1 and EAAT-2 gene expression as well as glutamate uptake in differentially activated macrophages and show that the effects of HIV are not directly related to pro- or anti-inflammatory mediators. Finally, this study shows that glutamate transport by macrophages is less affected than what has been described in astrocytes. Macrophages may thus play a role in neuroprotection against glutamate in the infected brain, through their expression of both EAATs and glutamine synthetase. Because glutamate metabolism by activated macrophages is sensitive to both HIV infection and inflammation, it may thus be of potential interest as a therapeutic target in HIV encephalitis.
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PMID:Glutamate metabolism in HIV-infected macrophages: implications for the CNS. 1668 72

Recombinant Listeria monocytogenes strains induce strong cellular immune responses and may prove useful for antigen delivery for the vaccination of humans. However, the genetic systems currently available for the stable expression of recombinant antigens by L. monocytogenes rely on the use of antibiotic resistance genes. We report on a derivative, pPL2dalGlnA, of the Listeria monocytogenes pPL2 integration vector that completely lacks drug resistance genes. The selectable markers in pPL2dalGlnA are glutamine synthetase (GlnA) and alanine racemase (Dal). This novel vector was stably maintained in auxotropic L. monocytogenes strains that normally require d-alanine. The pPL2dalGlnA vector also partially restored the ability of an L. monocytogenes Deltadal Deltadat strain to colonize the spleens and livers of infected mice. A novel, highly attenuated strain of L. monocytogenes with quadruple deletions was also engineered by deleting the L. monocytogenes actA and plcB virulence genes from a Deltadal Deltadat strain. Infection of mice with recombinants of this mutant strain that express the antigen from pPL2dalGlnA were shown to elicit CD8(+) T-cell responses to human immunodeficiency virus Tat. This vector system is thus useful for stable antigen expression and vaccination studies.
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PMID:Stable integration vector for nutrient broth-based selection of attenuated Listeria monocytogenes strains with recombinant antigen expression. 1865 Apr

Human immunodeficiency virus-associated sensory neuropathy (HIV-SN) remains a frequent neurologic complication of HIV infection. Little is known about alterations in the peripheral nervous system during the early stages of HIV, a time when neuroprotective interventions may be most beneficial. We performed Nanostring gene expression analysis on lumbar dorsal root ganglia (DRG) from 6 simian immunodeficiency virus (SIV)-infected pigtailed macaques killed at 7 days post-inoculation and 8 uninfected controls. We found significant upregulation of many genes involved in immune signaling and activation in the DRG. Among genes related to glutamate metabolism, there was significant upregulation of glutamine synthetase (GS), while glutaminase (GLS) was downregulated. Several genes involved in the oxidative stress response also showed significant differential regulation in the DRG of 7d SIV-infected animals, with superoxide dismutase-2 (SOD2) showing the greatest median fold change compared to controls. Novel findings in the DRG were compared to corresponding brain data and further investigated at the protein level by Western blotting and immunohistochemistry. Together with our previous finding of significant epidermal nerve fiber loss at 14 days post-SIV infection, results of this study demonstrate that immune activation and altered cellular metabolism at in the DRG precede and likely contribute to early sensory nerve injury in HIV-SN.
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PMID:SIV-Induced Immune Activation and Metabolic Alterations in the Dorsal Root Ganglia During Acute Infection. 3050 Sep 18