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)

Human immunodeficiency virus (HIV)-1 infectivity requires actin-dependent clustering of host lipid raft-associated receptors, a process that might be linked to Rho guanosine triphosphatase (GTPase) activation. Rho GTPase activity can be negatively regulated by statins, a family of drugs used to treat hypercholesterolemia in man. Statins mediate inhibition of Rho GTPases by impeding prenylation of small G proteins through blockade of 3-hydroxy-3-methylglutaryl coenzyme A reductase. We show that statins decreased viral load and increased CD4+ cell counts in acute infection models and in chronically HIV-1-infected patients. Viral entry and exit was reduced in statin-treated cells, and inhibition was blocked by the addition of l-mevalonate or of geranylgeranylpyrophosphate, but not by cholesterol. Cell treatment with a geranylgeranyl transferase inhibitor, but not a farnesyl transferase inhibitor, specifically inhibited entry of HIV-1-pseudotyped viruses. Statins blocked Rho-A activation induced by HIV-1 binding to target cells, and expression of the dominant negative mutant RhoN19 inhibited HIV-1 envelope fusion with target cell membranes, reducing cell infection rates. We suggest that statins have direct anti-HIV-1 effects by targeting Rho.
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PMID:Statins inhibit HIV-1 infection by down-regulating Rho activity. 1531 78

Use of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus (HIV) infection is associated with the development of cardiovascular risk factors, including dyslipidemia, insulin resistance, fat redistribution, and hypertension. The results of the Data Collection on Adverse Events of Anti-HIV Drugs study showed that HAART therapy is associated with a 26% relative risk increase in the rate of myocardial infarction per year of HAART exposure. A number of studies have shown that insulin resistance often precedes lipodystrophy, suggesting that insulin resistance may be a primary feature of the metabolic syndrome in this population. The rate-limiting step in the uptake of glucose is glucose transport, and the predominant glucose transporter (GLUT) in muscle and fat is GLUT-4. Specific protease inhibitors (PIs) have been associated with decreased GLUT-4-mediated glucose transport and insulin resistance both in vitro and in vivo, whereas newer protease inhibitors may have fewer effects on insulin sensitivity. Data also suggest that endothelial dysfunction, impaired fibrinolysis, and excess inflammation may contribute to increased cardiovascular risk in the population infected with HIV. Moreover, recent data suggest that evidence for coronary atherosclerotic disease can be revealed by means of carotid intimal medial thickness (IMT) assessments in specific groups of HIV patients. Pharmacologic strategies for the prevention and/or treatment of HAART-induced dyslipidemia and abnormal glucose homeostasis include 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), resins, nicotinic acid, fibrates, and insulin-sensitizing agents. However, newer PIs such as atazanavir may result in less insulin resistance and dyslipidemia and, as part of a HAART regimen, use of atazanavir may reduce the metabolic complications associated with HAART.
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PMID:Metabolic syndrome and cardiovascular disease in patients with human immunodeficiency virus. 1590 92

Increased deposition of amyloid beta (Abeta) is characteristic for normal aging and human immunodeficiency virus-1 (HIV-1)-associated alterations of the central nervous system. In addition, both Abeta and HIV-1 are known to induce cellular oxidative stress and disruption of the blood-brain barrier (BBB). Therefore, we hypothesize that Abeta and HIV-1 protein Tat can potentiate their proinflammatory effects at the brain endothelium level. To address this hypothesis, we studied promoter activity of three proinflammatory genes in an in vitro BBB model of human brain microvascular endothelial cells (HBMEC) cocultured with a human astrocyte cell line producing Tat (SVGA-Tat cells) and exposed to Abeta. Treatment of HBMEC with Abeta(1-40) in the presence of SVGA-Tat cells resulted in a significant up-regulation of E-selectin, CC chemokine ligand-2, and interleukin-6 promoter activities and protein levels compared with the individual effects of Abeta or Tat. In addition, Abeta markedly amplified E-selectin promoter activity in HBMEC cocultured with HIV-1-infected Jurkat T cells. Simvastatin, the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, effectively blocked proinflammatory reactions induced by Abeta in cocultures with SVGA-Tat cells or with HIV-1-infected Jurkat cells. The present study indicates that a combined exposure to Abeta and Tat or HIV-1 can synergistically potentiate the expression of inflammatory genes in brain endothelial cells. In addition, simvastatin may provide a beneficial influence by reducing these effects at the BBB level.
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PMID:Simvastatin protects against amyloid beta and HIV-1 Tat-induced promoter activities of inflammatory genes in brain endothelial cells. 1827 75