Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To establish whether the high plasma glutamate and low acid-soluble thiol (mainly cysteine) concentrations previously found in patients with HIV-1 infection are a consequence of the infection or a risk factor for its development, a closely related animal model, rhesus and fascicularis macaques infected with simian immunodeficiency virus (SIVmac251), was studied. The 23 infected macaques had significantly lower mean plasma thiol and higher glutamate concentrations than 18 uninfected controls (p less than 0.001). The changes were apparent by 1 week after infection. Thus, abnormal plasma glutamate and thiol concentrations are, at least in this model, a direct and early consequence of the retroviral infection.
...
PMID:Metabolic disorder as early consequence of simian immunodeficiency virus infection in rhesus macaques. 168 16

In order to determine whether the cysteine requirement of human T lineage cells is met primarily by extracellular cysteine or by cystine, amino-acid-transport activities were measured in resting and mitogenically stimulated human peripheral blood lymphocytes (PBL) and several human T cell clones and T cell tumors. The transport activity of the small neutral amino acids cysteine and alanine (ASC system) and the transport of the cationic amino acid arginine (y+ system) were found to be markedly increased after stimulation of PBL by the T cell mitogen phytohemagglutinin from Phaseolus vulgaris. The anionic transport activity for cystine and glutamate (Xc- system), in contrast, was extremely weak in both resting and activated human PBL and also in all human T cell lines under test. The weak system Xc- activity of human T lineage cells was further confirmed by an independent line of experiments showing that an increase of the extracellular concentration of glutamate, i.e. a competitive inhibitor of cystine transport, causes a decrease in the intracellular cystine levels in cells of the promonocytic line U937, but not in T lineage cells (Molt-4). A third set of experiments showed that the rate of DNA synthesis in mitogenically stimulated human PBL is strongly influenced by variations of the extracellular cysteine level, even in cultures with relatively high and approximately physiological concentrations of cystine. Cysteine cannot be replaced in this case by the addition of corresponding amounts of cystine or methionine. This demonstrates an important functional consequence of the weak cystine transport activity of human lymphocytes. The results may be relevant for the pathogenetic mechanism of the acquired immunodeficiency syndrome, since the mean plasma cysteine concentration of human-immunodeficiency-virus-1-seropositive persons was found to be strongly decreased in comparison with that of healthy blood donors, and since the cysteine level even of healthy persons is extremely low in comparison with all other protein-forming amino acids.
...
PMID:Low membrane transport activity for cystine in resting and mitogenically stimulated human lymphocyte preparations and human T cell clones. 168 Jun 78

The effects of glutathione (GSH), glutathione ester (GSE), and N-acetyl-L-cysteine (NAC) on the induction of human immunodeficiency virus (HIV) expression were investigated in the chronically infected monocytic U1 cell line, a previously described cellular model for HIV latency. U1 cells constitutively express low levels of virus, which can be increased by phorbol 12-myristate 13-acetate (PMA), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and other inducers. GSH, GSE, and NAC suppressed in a dose-dependent fashion the induction of HIV expression mediated by PMA, TNF-alpha, and IL-6, in the absence of cytotoxic or cytostatic effects. Reverse transcriptase activity, inducible by PMA, TNF-alpha, or IL-6, was decreased by 80-90% after pretreatment with GSH, GSE, or NAC. The induction of total HIV protein synthesis was also decreased appreciably after pretreatment with GSH, GSE, or NAC. The accumulation of HIV mRNA was substantially suppressed after pretreatment with NAC but to a lesser extent after pretreatment with GSH or GSE. Although PMA induces the expression of TNF-alpha in U1 cells, the suppressive effect of GSH, GSE, and NAC on PMA-induced HIV expression in U1 cells was not associated with the inhibition of TNF-alpha expression. The present findings, which elucidate relationships between cellular GSH and HIV expression, suggest that therapy with thiols may be of value in the treatment of HIV infection.
...
PMID:Suppression of human immunodeficiency virus expression in chronically infected monocytic cells by glutathione, glutathione ester, and N-acetylcysteine. 170 37

The enzyme reverse transcriptase (RT) is crucial in the early steps of the life cycle of retroviruses. We have expressed in bacteria the RTs from human immunodeficiency viruses (HIV) types 1 and 2 in order to study the structural-functional relationships of these two multifunctional enzymes that share a relatively high degree of amino acid sequence homology. For comparison purposes, we have analyzed several catalytic functions of both enzymes. The two HIV RTs show a high similarity in many aspects studied but exhibit profound differences in several other properties. For instance, the specific RNase H activity of HIV-2 RT is about 10 times lower than the corresponding activity of HIV-1 RT. There are also significant dissimilarities between some of the apparent Km values calculated for the DNA polymerizing functions of both enzymes. Furthermore, the heat stability of the DNA polymerizing activity of HIV-2 RT is about 15-fold higher than that of HIV-1 RT. On the other hand, the susceptibility of the RNase H activities of the two enzymes to heat inactivation was found to be similar. Other treatments also enable discrimination between the RNase H and DNA polymerizing catalytic properties of the two enzymes (although both reverse transcriptases respond similarily). Thus, the RNase H activity was inactivated by N-ethylmaleimide, suggesting the possible involvement of cysteine residues in performing this activity, whereas the DNA polymerizing functions of the two enzymes were fully resistant to this chemical modification. The zinc chelator 1,10-phenanthroline affected the DNA polymerase activities of both enzymes to a significantly higher extent than the RNase H activity. In all, the two HIV RTs were shown to be substantially different one from the other in several of their properties and also distinct from other RTs thus far studied.
...
PMID:Catalytic properties of the reverse transcriptases of human immunodeficiency viruses type 1 and type 2. 170 12

All animal retroviruses whose nucleotide sequences have been determined contain two or three closely spaced cysteine residues in the extracellular domain of the env-encoded transmembrane protein. Using human immunodeficiency virus type 1 gp41 as a working model, the functional significance of these highly conserved cysteines was investigated. We report here that substituting the two conserved cysteine residues in this domain of gp41 with glycine residues resulted in the loss of viral infectivity, which could be attributed to severe impairment in the processing of gp160 precursor to gp120.
...
PMID:Role of conserved gp41 cysteine residues in the processing of human immunodeficiency virus envelope precursor and viral infectivity. 171 22

To elucidate the action of vitamin C on pathogenic human retroviruses, we investigated and compared the effects of noncytoxic concentrations of ascorbic acid (AA), its calcium salt (Ca-ascorbate), and two thiol-based reducing agents [glutathione (GSH) and N-acetyl-L-cysteine (NAC)] against human immunodeficiency virus (HIV)-1 replication in chronically infected T lymphocytes. Ca-ascorbate reduced extracellular HIV reverse transcriptase (RT) activity by about the same magnitude as the equivalent dose of AA. Long-term experiments showed that continuous presence of ascorbate was necessary for HIV suppression. NAC (10 mmol/L) caused less than twofold inhibition of HIV RT and conferred a synergistic effect (approximately eightfold inhibition) when tested simultaneously with AA (0.426 mmol/L). In contrast, nonesterified GSH (less than or equal to 1.838 mmol/L) had no effect on RT concentrations and did not potentiate the anti-HIV effect of AA. These results further support the potent antiviral activity of ascorbate and suggest its therapeutic value in controlling HIV infection in combination with thiols.
...
PMID:Comparative study of the anti-HIV activities of ascorbate and thiol-containing reducing agents in chronically HIV-infected cells. 172 May 98

We have recently described a nonnucleoside compound that specifically inhibits the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS. This compound, nevirapine (BI-RG-587), interacts with highly conserved tyrosine residues at positions 181 and 188 in the reverse transcriptase to inhibit the recombinant enzyme and virus replication in cell culture with 50% inhibitory concentrations in the 40 nM range. HIV-1 variants resistant to nevirapine emerged with passage in cell culture in the presence of drug. This resistant phenotype was stable with continued passage in the absence of drug. These mutants had a substitution of cysteine for the tyrosine at position 181. Introduction of this mutation into the recombinant enzyme increased the inhibitory concentration of nevirapine 100-fold. Substitution of cysteine for tyrosine at residue 181 into the wild-type viral genome conferred a similar reduction in susceptibility to nevirapine. Mutants were also resistant to a tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one and -thione derivative and two 6-phenylthiouracil derivatives but retained their sensitivity to the other reverse transcriptase inhibitors, 3'-azido-3'-deoxythymidine and foscarnet.
...
PMID:Human immunodeficiency virus type 1 mutants resistant to nonnucleoside inhibitors of reverse transcriptase arise in tissue culture. 172 24

The transmembrane (TM) protein of human immunodeficiency virus type 1 has been demonstrated to be involved in viral infectivity and syncytium formation. Two highly conserved cysteine residues in the extracellular region of the TM protein are shown to be essential for processing the 160-kDa envelope precursor into the active 120- and 41-kDa mature forms.
...
PMID:Conserved cysteine residues in the human immunodeficiency virus type 1 transmembrane envelope protein are essential for precursor envelope cleavage. 173 Oct 99

The nucleotide sequence of the pol-env intergenic region of two isolates of caprine arthritis-encephalitis virus (CAEV) was determined. Two open reading frames (orfs) were identified, designated Q and S by homology with visna virus. CAEV orf S is a single exon encoding a deduced 87-amino acid gene product sharing 36 amino acid identities with the visna trans-acting transcriptional activator (Tat). Ten of these identities comprise a conserved CGCRLCNPGW sequence similar to a cysteine-rich domain essential for trans-activation by human immunodeficiency virus Tat. To determine if transcription promoted by the CAEV long terminal repeat (LTR) could be stimulated in CAEV-infected goat synovial membrane cells, a plasmid (pCAE-CAT) expressing bacterial chloramphenicol acetyltransferase (CAT) under control of the CAEV LTR was transfected into uninfected and infected cells. Sixfold enhancement of CAT activity was observed in infected cells using 100 ng of transfected plasmid. To determine if the pol-env region encodes a gene product which trans-activates the CAEV LTR, goat synovial membrane cells were cotransfected with pCAE-CAT and pRSV-1.9, a plasmid expressing the pol-env region under control of the Rous sarcoma virus LTR. Results indicated that the CAEV genome encodes a tat gene product attributable to orf S.
...
PMID:Genetic structure of the pol-env region of the caprine arthritis-encephalitis lentivirus genome. 184 32

In this study, enzyme immunoassays for detection of type-specific antibodies to human immunodeficiency viruses (HIV) were developed by using short peptides corresponding to sequences located within the immunodominant domain of the transmembrane glycoproteins of both HIV-1 and HIV-2-simian immunodeficiency virus (SIV). The assays were highly sensitive with currently available sera from various geographical areas. Furthermore, they appeared to be more specific in HIV serotyping than the Western blot (immunoblot) assay, since all of the sera were clearly discriminated as one or the other type. It was also shown that in contrast to HIV-1, the C-terminal cysteine residue (amino acid 620, SIV from captive macaques, Mm142 strain) of the HIV-2-SIV peptide is not necessary for recognition of the peptide by antibody to HIV-2.
...
PMID:Fine serotyping of human immunodeficiency virus serotype 1 (HIV-1) and HIV-2 infections by using synthetic oligopeptides representing an immunodominant domain of HIV-1 and HIV-2/simian immunodeficiency virus. 188 33


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---