Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A previously isolated partial cDNA encoding a cell wall protein antigen found on hyphal surfaces of the opportunistic fungal pathogen, Candida albicans (Staab et al., 1996) was used to clone the complete hyphal wall protein 1 gene (HWP1). Hyphal forms of C. albicans invade mucosal surfaces of immunocompromised patients such as those with AIDS. HWP1 consisted of an open reading frame predicting an acidic protein (pI of 3.37) with a calculated molecular size of 61,122. The antigenic domain was located in the N-terminal third of the protein. The remainder of the protein contained abundant hydroxy amino acids, and terminated with a string of 15 amino acids typical of sequences specifying post-translational modification with glycosylphosphatidylinositol (6PI). The analyses suggested that Hwp1 is a glucan-linked protein with serine/threonine-rich regions that are predicted to function in extending a ligand-binding domain into the extracellular space.
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PMID:Genetic organization and sequence analysis of the hypha-specific cell wall protein gene HWP1 of Candida albicans. 963 15

Polymorphisms in genes encoding transporters associated with antigen processing (TAP) have been associated with heterogeneity of disease progression in HIV-1-infected homosexual men. In our recent AIDS-related studies of cohorts from Rwanda and Zambia, four new polymorphic sites in the TAP2 coding region were detected by single-strand conformation polymorphism (SSCP) and confirmed by bi-directional nucleotide sequencing and restriction enzyme digestion. The first, a substitution of Thr (GCC) for Ala (ACC) at codon position 374 in exon 5, was found in about 13% of Rwandans and Zambians (n=213). The remaining 3 new polymorphisms were seen in the 7th exon with changes of 458Thr-ACG to ACA, 466Gly-GGG to GGA, and 467Val-GTT to Ile-ATT, respectively These 3 variants occurred exclusively on the same chromosome and appeared to have arisen together from the 374Thr-bearing allele. Analyses of the relationship between the 374Thr-467Ile segment and the nearby markers in DQB1 and DRB1 suggested the existence of a unique extended haplotype related to these newly identified variants.
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PMID:New TAP2 polymorphisms in Africans. 967 56

This study was conducted to identify the most rate-limiting amino acids for whole-body protein synthesis in acquired immunodeficiency syndrome (AIDS) patients. We postulated that an essential amino acid that would be rate limiting in AIDS should have a low basal plasma concentration and should remain at a low level during amino acid infusion. Seven male AIDS patients (median age 37 y, CD4 cell count: 76 mm-3) without any clinically active opportunistic infection during the month before the experiment were infused intravenously with a complete amino acid-glucose mixture for 2.5 h. Eight healthy volunteers were used as controls. Before the infusion, the concentrations of most free essential amino acids (methionine, threonine, histidine, isoleucine, leucine and tryptophan) were significantly lower (P < 0.05) in AIDS patients than in controls. Most plasma free essential amino acids increased significantly during infusion. However, the absolute increase above basal levels for threonine, valine, lysine, (P < 0.05) and methionine (P < 0.073) was smaller in AIDS patients than in control subjects. Thus, threonine and possibly methionine may be rate limiting for whole-body protein synthesis in AIDS patients, suggesting that there are selective amino acid requirements in patients with AIDS.
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PMID:Threonine and methionine are limiting amino acids for protein synthesis in patients with AIDS. 968 54

At least 1.5 million children worldwide are infected with HIV-1. Most HIV-infected children obtained the virus from their mother either in utero, at delivery, or postpartum through breast-feeding. Since the V3 loop of HIV is an important determinant for viral neutralization and cellular tropism, mutations in the V3 region could possibly affect mother-to-child transmission. Serum specimens from 17 HIV-1-seropositive mother-child pairs being treated at the pediatric clinic of Siriraj Hospital, Bangkok, in 1994 and 1995, were studied to better understand the genetic characteristics of HIV-1 subtype E involved in vertical transmission. The V3 regions of HIV-1 subtype E isolated from the subjects at 1 month after birth were sequenced after being cloned into pCRII vectors, with at least 3 clones of each sample collected. All mothers were asymptomatic and had been infected through a heterosexual route. 9 infants were mildly symptomatic and had evidence of immunosuppression during their first year of life. The nucleotide sequences of asymptomatic infants were significantly closer to maternal sequences than those of the AIDS cases. The data suggest that 1 or 2 genotypes from the mother were selected, transmitted to the infant, and then became diverse. The substitution with asparagine at threonine at position 13 and aspartic acid at position 29 of the V3 sequence were significantly associated with nonimmunosuppression during the first year of life.
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PMID:V3 sequence diversity of HIV-1 subtype E in infected mothers and their infants. 970 37

Infection with the human immunodeficiency virus (HIV) frequently is complicated with thrombocytopenia (HIV-Thr) during all stages of the infection. The treatments for autoimmune thrombocytopenic purpura (ITP) are used in HIV-Thr; however, their effects upon the immune status of patients with acquired immunodeficiency syndrome (AIDS) are unknown. Intravenous immunoglobulin (IVIg) is used in patients with ITP and HIV-Thr; however, its usefulness in thrombocytopenic AIDS patients has not been directly addressed. We used a low-dose IVIg regimen (0.04 g/kg per week during five weeks) for the treatment of HIV-Thr complicating AIDS. Thirteen patients received IVIg. We observed a response to IVIg in 13 patients by the end of week one and in 10 patients by the end of week five. Long-term response, evaluated three months after stopping IVIg, was present in four cases. IVIg was well tolerated and no opportunistic infections were observed during the study period. Compared with previous reports, we used 10% of the previously proposed dosage with an important decrease in the cost of treatment. Our results suggest that this low-dose IVIg regimen is a highly effective, nonexpensive alternative in treating HIV-Thr in AIDS. If sustained responses can be obtained with a similar low-dose maintenance regimen, IVIg may be the first choice for the treatment of HIV-Thr in AIDS patients.
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PMID:Usefulness of a low-dose intravenous immunoglobulin regimen for the treatment of thrombocytopenia associated with AIDS. 976 97

An important component of triple-drug anti-AIDS therapy is 2', 3'-dideoxy-3'-thiacytidine (3TC, lamivudine). Single mutations at residue 184 of the reverse transcriptase (RT) in HIV cause high-level resistance to 3TC and contribute to the failure of anti-AIDS combination therapy. We have determined crystal structures of the 3TC-resistant mutant HIV-1 RT (M184I) in both the presence and absence of a DNA/DNA template-primer. In the absence of a DNA substrate, the wild-type and mutant structures are very similar. However, comparison of crystal structures of M184I mutant and wild-type HIV-1 RT with and without DNA reveals repositioning of the template-primer in the M184I/DNA binary complex and other smaller changes in residues in the dNTP-binding site. On the basis of these structural results, we developed a model that explains the ability of the 3TC-resistant mutant M184I to incorporate dNTPs but not the nucleotide analog 3TCTP. In this model, steric hindrance is expected for NRTIs with beta- or L- ring configurations, as with the enantiomer of 3TC that is used in therapy. Steric conflict between the oxathiolane ring of 3TCTP and the side chain of beta-branched amino acids (Val, Ile, Thr) at position 184 perturbs inhibitor binding, leading to a reduction in incorporation of the analog. The model can also explain the 3TC resistance of analogous hepatitis B polymerase mutants. Repositioning of the template-primer as observed in the binary complex (M184I/DNA) may also occur in the catalytic ternary complex (M184I/DNA/3TCTP) and contribute to 3TC resistance by interfering with the formation of a catalytically competent closed complex.
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PMID:Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids. 1046 56

Early detection of viral mutations, particularly those mutations associated with cross-resistance to antiretroviral drugs, is critical both for understanding the mechanism of drug resistance and for the clinical management of patients infected with HIV-1. One of the frequently observed mutations in the HIV-1 reverse transcriptase (RT)-coding region is ACC --> TAC at codon 215, resulting in a change of wild-type threonine (T) to tyrosine (Y); this mutation has been associated with decreased phenotypic susceptibility to zidovudine (ZDV). We describe a technique for the detection of the T215Y mutation using reverse transcription-polymerase chain reaction (RT-PCR) amplification of viral sequences and a 5' nuclease assay requiring fluorogenic probes. In addition to detecting the presence of the ACC --> TAC mutation at codon 215, this assay provides an increased ability to detect low levels of mutant species in a mixed population, relative to conventional sequencing. Further advantages of this technique include the rapid and high-throughput nature of the assay, the accuracy of the assay relative to conventional DNA sequencing, and the convenience of combining RT-PCR virus amplification with the allelic discrimination assay, without the need for purification of PCR products.
AIDS Res Hum Retroviruses 1999 Sep 20
PMID:Rapid detection of the HIV type 1 reverse transcriptase codon T215Y by reverse transcription-polymerase chain reaction with fluorogenic probes. 1050 77

The genetic makeup of animal and plant populations is determined by established principles and concepts. Ecology and evolution provide a basic theoretical framework for understanding how genetic changes occur in populations. Whether these rules can be applied to host retroviral populations is unknown. Individuals infected with the human immunodeficiency virus (HIV) contain within their bodies a viral population. This population is known as a viral quasispecies. Located in the transmembrane protein of HIV-1 is the viral sequence Gly-Thr-Asp-Arg-Val. Previous immunological studies have shown that viral antibody is produced in response to this five-amino-acid sequence. Antibody to this viral sequence also crossreacts and binds to a related peptide sequence found on certain immune cells. This related sequence, Gly-Thr-Glu-Arg-Val, is found on immune cells bearing a structure known as the major histocompatibility complex (MHC). The viral transmembrane sequence, Gly-Thr-Asp-Arg-Val, can be substituted with alanine residues utilizing site-directed mutagenesis. This creates a viral clone devoid of the genetic similarity with the MHC. Chimpanzees progressing to AIDS contain both sequences of interest. Suppression of the chimpanzee quasispecies utilizing anti-retroviral drugs is proposed. This action serves to suppress the presence of the viruses containing the sequence Gly-Thr-Asp-Arg-Val. When viral load has been reduced significantly, a drug resistant, alanine altered clone is to be introduced in large numbers. The concept of evolutionary stable strategy predicts that a viable HIV clone with alanine residues can genetically dominate the viral population. Immune system recognition of the alanine sequence is likely to result in renewed antibody production. Antibodies to the alanine containing viral sequence should not recognize or bind to the MHC. Immunological parameters can then be measured to determine the physiological impact of eliminating a sequence responsible for molecular mimicry between virus and host.
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PMID:Evolutionary stable strategy: a test for theories of retroviral pathology which are based upon the concept of molecular mimicry. 1066 Apr 76

Peptide T has a sequence (Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr) belonging to HIV envelope that is involved in the interaction with CD(4) receptor of T lymphocytes. Research of protease activities towards this peptide is very relevant for AIDS therapy. Characterization of specificity of subtilisin Carlsberg towards this very hydrophilic peptide is proposed by using high-performance liquid chromatography and mass spectrometry. Peptide T was totally hydrolysed by the protease after 24 h. Separation of hydrophilic fragments was perfected with an hydrophilic stationary phase and a reversed acetonitrile gradient. Peptide masses were determined by ion spray mass spectrometry. Four primary and one secondary hydrolysis products were found, corresponding to cleavage at the carboxylic side of threonine. Specifities of subtilisin Carlsberg towards the Segments 19 to 26 of bovine pancreatic ribonuclease A, an homologous fragment of peptide T, and peptide T were compared.
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PMID:Characterization of specificity of subtilisin Carlsberg towards peptide T by high-performance liquid chromatography and electrospray mass spectrometry. 1071 10

Many functional glycoproteins are expressed on the lymphocyte cell surface. Some of them carry O-linked oligosaccharides (O-glycans), which are conjugated through serine or threonine residues. During various biological processes, including T-cell activation, a tetrasaccharide on the T-cell surface is dramatically converted to a branched hexasaccharide, called core2 O-glycan. The same structural change in O-glycans is also found on the lymphocytes from patients with immunodeficiency conditions such as Wiskott-Aldrich syndrome and AIDS. Several studies revealing the roles of core2 O-glycans in immune responses show that this is a biologically significant change. In particular, core2 O-glycans expressed on the cell surface reduce cell-cell interactions, thereby regulating immune responses. Furthermore, core2 O-glycan is a key backbone structure in forming selectin ligands. Thus, O-linked oligosaccharides, in particular those containing core2 branches, play vital roles in immune responses and may play dual roles in certain situations. This review will summarize the results obtained from various studies investigating the roles of O-glycans in immunological processes. BioEssays 23:46-53, 2001.
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PMID:Roles of O-linked oligosaccharides in immune responses. 1113 8


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