Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on theoretical evidence, it has been proposed that HIV-1 may encode several selenoprotein modules, one of which (overlapping the env gp41-coding region) has highly significant sequence similarity to the mammalian selenoprotein glutathione peroxidase (GPx; EC ). The similarity score of the putative HIV-1 viral GPx homolog relative to an aligned set of known GPx is 6.3 SD higher than expected for random sequences of similar composition. Based on that alignment, a molecular model of the HIV-1 GPx was constructed by homology modeling from the bovine GPx crystal structure. Despite extensive truncation relative to the cellular GPx gene, the structural core and the geometry of the catalytic triad of selenocysteine, glutamine, and tryptophan are well conserved in the viral GPx. All of the insertions and deletions predicted by the alignment proved to be structurally feasible. The model is energetically favorable, with a computed molecular mechanics strain energy close to that of the bovine GPx structure, when normalized on a per-residue basis. However, considering the remote homology, this model is intended only to provide a working hypothesis allowing for a similar active site and structural core. To validate the theoretical predictions, we cloned the hypothetical HIV-1 gene and found it to encode functional GPx activity when expressed as a selenoprotein in mammalian cells. In transfected canine kidney cells, the increase in GPx activity ranged from 21% to 43% relative to controls (average 30%, n = 9, P < 0.0001), whereas, in transfected MCF7 cells, which have low endogenous GPx activity, a near 100% increase was observed (average 99%, n = 3, P < 0.05).
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PMID:Molecular modeling and in vitro activity of an HIV-1-encoded glutathione peroxidase. 1084 44

There is considerable literature demonstrating that specific nutrients can influence immune function in health and disease. This review will examine the literature and the rational for classifying two amino acids, glutamine (gln) and arginine (arg), as "immunonutrients" during infections. An understanding of immune defenses during infections (virus, parasite, bacteria, protozoa) and metabolism of gln and arg by immune cells is necessary to understand how these nutrients can influence specific functions of the immune system. This review focuses on several key clinical studies in immunosuppressed individuals (burn patients, individuals with cancer and HIV infection, and those undergoing surgery or who have experienced major traumas) that have tested the hypothesis that the provision of gln and/or arg is beneficial to immune function and clinical outcome. These clinical studies support the dietary "essentiality" of these two nutrients for improving immune responses in most immunosuppressive states associated with high rates of infection. However, the role of these nutrients in modulating the immune changes that occur with exercise in healthy athletes demands additional experiments.
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PMID:Glutamine and arginine: immunonutrients for improved health. 1091 Feb 94

The role of antioxidants in preventing apoptosis and viral activation in HIV is well documented. N-acetylcysteine, glutathione, and alpha-lipoic acid have been shown to interrupt the process of viral activation and CD4 cell death. L-glutamine has been shown to improve glutathione levels and significantly increase lean body mass in HIV infection. The literature on the use of L-carnitine and acetyl-L-carnitine in treating mitochondrial toxicity, both in muscle and nerve pathologies is relevant in nutritional treatment of HIV, given the mitochondrial toxicity of nucleoside analog reverse transcriptase inhibitor therapy. The current use of highly active antiviral therapies, their toxicity, and significant failure rates have created the need for a more conservative reassessment of HIV treatment. The adjunctive use of nutrient therapy in the treatment of HIV is reviewed here.
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PMID:Nutrients and HIV: part three - N-acetylcysteine, alpha-lipoic acid, L-glutamine, and L-carnitine. 1095 77

HIV-infected injection drug users (IDUs) often suffer from serious nutritional deficiencies. This is a concern because plasma levels of micronutrients such as vitamin B12, zinc, and selenium have been correlated with mortality risk in HIV-positive populations. Injection drug use also increases lipid peroxidation and other indicators of oxidative stress, which, combined with antioxidant deficiencies, can stimulate HIV-1 replication through activation of NF-kappaB transcription factors, while weakening immune defenses. As detailed herein, these prooxidant stimuli can also increase the pathogenic effects of HIV-1 by another mechanism, involving viral selenoproteins. Overlapping the envelope coding region, HIV-1 encodes a truncated glutathione peroxidase (GPx) gene (see #6 in reference list). Sequence analysis and molecular modeling show that this viral GPx (vGPx) module has highly significant structural similarity to known mammalian GPx, with conservation of the catalytic triad of selenocysteine (Sec), glutamine, and tryptophan. In addition to other functions, HIV-1 vGPx may serve as a negative regulator of proviral transcription, by acting as an NF-kappaB inhibitor (a known property of cellular GPx). Another potential selenoprotein coding function of HIV-1 is associated with the 3' end of the nef gene, which terminates in a conserved UGA (potential Sec) codon in the context of a sequence (Cys-Sec) identical to the C-terminal redox center of thioredoxin reductase, another cellular regulator of NF-kappaB. Thus, in combination with known cellular mechanisms involving Se, viral selenoproteins may represent a unique mechanism by which HIV-1 monitors and exploits an essential micronutrient to optimize its replication relative to the host.
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PMID:Nutrition, HIV, and drug abuse: the molecular basis of a unique role for selenium. 1112 28

The HIV transactivator, Tat, has been shown to be capable of potent repression of transcription initiation. Repression is mediated by the C-terminal segment of Tat, which binds the TFIID component, TAF(II)250, although the site(s) of interaction were not defined previously. We now report that the interaction between Tat and TAF(II)250 is extensive and involves multiple contacts between the Tat protein and TAF(II)250. The C-terminal domain of Tat, which is necessary for repression of transcription initiation, binds to a segment of TAF(II)250 that encompasses its acetyl transferase (AT) domain (885-1034 amino acids (aa)). Surprisingly, the N-terminal segment of Tat, which contains its activation domains, also binds to TAF(II)250 and interacts with two discontinuous segments of TAF(II)250 located between 885 and 984 aa and 1120 and 1279 aa. Binding of Tat to the 885-984 aa segment of TAF(II)250 requires the cysteine-rich domain of Tat, but not the acidic or glutamine-rich domains. Binding by the N-terminal domain of Tat to the 1120-1279 aa TAF(II)250 segment does not involve the acidic, cysteine- or glutamine-rich domains. Repression of transcription initiation by Tat requires functional TAF(II)250. We now demonstrate that transcription of the HIV LTR does not depend on TAF(II)250 which may account for its resistance to Tat mediated repression.
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PMID:Extensive interactions between HIV TAT and TAF(II)250. 1125 18

A new outpatient trial is studying glutamine as a treatment for leaky bowel syndrome associated with HIV infection. Participants will be given urine tests and a 15 to 20 minute biopsy which is done by swallowing a small capsule (after numbing the throat) to see if it goes into the intestine; the capsule is then pulled out. After biopsy, the groups are divided into glutamine treatment groups with one placebo group. After 28 days, permeability tests and biopsies are redone.
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PMID:Bowel syndrome. 1136 87

Nutrition specialist Lark Lands produced a set of recommendations on preventing wasting through nutritional supplements and a healthy diet. Her recommendations include citrates, fumarates, malates, aspartates, ascorbates, glycinates, and picolinates. People with HIV tend to have low levels of L-glutamine, an amino acid needed to build muscle, and supplemental doses will help prevent wasting.
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PMID:Nutritional intervention to prevent wasting. 1136 22

Glutamine, a nutritional supplement, has been acclaimed to stop diarrhea and wasting, enhance muscularity, promote immune cell growth, and possibly slow HIV progression. It is most commonly used with anti-oxidants, which help relieve oxidative stress and neutralize chemicals that are built up in the bloodstream as a result of the immune response to HIV. A Harvard researcher noted that patients supplemented by glutamine did not develop an extended belly associated with use of some protease inhibitors. In addition, there appears to be no toxicity from glutamine. Two case studies of people who take glutamine are profiled. Recommended dosages and administration are provided.
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PMID:Glutamania-is there anything Glutamine doesn't do? 1136 95

The changes in nutritional needs of the body as HIV progresses are discussed. Nutrition, food preparation, and supplements are areas where one can meet those changing needs. For instance, as HIV progresses, the body needs more calories and subsequently needs more protein to build lean body mass. Supplements of the amino acid L-glutamine can help with this. Resistance exercise and anabolic steroids also help to reverse wasting. One side effect of protease inhibitors is a surplus of fat in the blood. A list of vitamin supplements that lessen the cardiovascular risk from this excess fat is provided. Tips are provided for combating low energy and lack of appetite. Ideas for managing lactose intolerance are given and vegetarians are reminded to get enough vitamin B-12. Recommendations for maintaining food safety and water safety are provided. The importance of vitamin and mineral supplements is discussed and a chart provides recommended doses.
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PMID:Nutrition know-how. 1136 85

The transmembrane subunit (TM) of human immunodeficiency virus type 1 (HIV-1) envelope protein contains four well-conserved sites for the attachment of N-linked carbohydrates. To study the contribution of these N-glycans to the function of TM, we systematically mutated the sites individually and in all combinations and measured the effects of each on viral replication in culture. The mutants were derived from SHIV-KB9, a simian immunodeficiency virus/HIV chimera with an envelope sequence that originated from a primary HIV-1 isolate. The attachment site mutants were generated by replacing the asparagine codon of each N-X-S/T motif with a glutamine codon. The mobilities of the variant transmembrane proteins in sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggested that all four sites are utilized for carbohydrate attachment. Transfection of various cell lines with the resulting panel of mutant viral constructs revealed that the N-glycan attachment sites are largely dispensable for viral replication. Fourteen of the 15 mutants were replication competent, although the kinetics of replication varied depending on the mutant and the cell type. The four single mutants (g1, g2, g3, and g4) and all six double mutants (g12, g13, g14, g23, g24, and g34) replicated in both human and rhesus monkey T-cell lines, as well as in primary rhesus peripheral blood mononuclear cells. Three of the four triple mutants (g124, g134, and g234) replicated in all cell types tested. The triple mutant g123 replicated poorly in immortalized rhesus monkey T cells (221 cells) and did not replicate detectably in CEMx174 cells. However, at 3 weeks posttransfection of 221 cells, a variant of g123 emerged with a new N-glycan attachment site which compensated for the loss of sites 1, 2, and 3 and resulted in replication kinetics similar to those of the parental virus. The quadruple mutant (g1234) did not replicate in any cell line tested, and the g1234 envelope protein was nonfunctional in a quantitative cell-cell fusion assay. The synthesis and processing of the quadruple mutant envelope protein appeared similar in transient assays to those of the parental SHIV-KB9 envelope. Given their high degree of conservation, the four N-linked carbohydrate attachment sites on the external domain of gp41 are surprisingly dispensable for viral replication. The viral variants described in this report should prove useful for investigation of the contribution of carbohydrate moieties on gp41 to recognition by antibodies, shielding from antibody-mediated neutralization, and structure-function relationships.
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PMID:Conserved, N-linked carbohydrates of human immunodeficiency virus type 1 gp41 are largely dispensable for viral replication. 1168 24


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