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)

In order to determine if viral selection occurs during mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1), we used a direct solid-phase sequencing method to sequence the p17 matrix protein-encoding regions of viral isolates from 12 HIV-1-infected mother-and-child pairs, 4 infected infants, 4 transmitting mothers, and 22 nontransmitting mothers and compared the sequences. The blood samples were collected during the delivery period for the mothers and during the first month of life for most of the children. The p17 nucleic sequences were distributed among several clades corresponding to the HIV-1 A, B, and G subtypes. At the amino acid level, no significant differences within the known p17 functional regions were observed among the subtypes. Statistical analyses could be performed with the B subtype. Within the major p17 antibody binding site, a constant KIEEEQN motif (amino acids 103 to 109) was found in all mother-and-child isolates from the B subtype. On the other hand, 9 of 17 nontransmitting mother isolates were variable in this 103 to 109 region. Thus, this motif was significantly associated with the transmitting status (chi square, P = 0.0034). A valine residue at position 104 was significantly associated with the nontransmitting phenotype (chi square, P = 0.014), suggesting that it has a protective role during vertical transmission. The C-terminal end of p17 was globally conserved among nontransmitting mother isolates (chi square, P = 0.0037). These results might improve the understanding of the pathogenesis of HIV-1 vertical transmission and might allow the screening of seropositive mothers by a rapid molecular or peptide test.
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PMID:Characterization of human immunodeficiency virus type 1 p17 matrix protein motifs associated with mother-to-child transmission. 867 72

The active human immunodeficiency virus type 1 (HIV-1) protease has a homodimeric structure, the subunits are connected by an 'interface' beta-sheet formed by the NH2- and COOH-terminal amino acid segments. Short peptides derived from these segments are able to inhibit the protease activity in the range of micromolar IC50 values. We have further improved the inhibitory power of such peptides by computer modelling. The best inhibitor, the palmitoyl-blocked peptide Pam-Thr-Val-Ser-Tyr-Glu-Leu, has an IC50 value of less than 1 microM. Some of the peptides also showed very good inhibition of the HIV-2 protease. The C-terminal segment of the HIV-1 matrix protein, Acetyl-Gln-Val-Ser-Gln-Asn-Tyr, also inhibits HIV-1 protease. Kinetic studies confirmed the 'dissociative' mechanism of inhibition by the peptides. Depending on the peptide structure and ionic strength, both dimerization inhibition and competitive inhibition were observed, as well as synergistic effects between competitive inhibitors and interface peptides.
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PMID:The inhibition of human immunodeficiency virus proteases by 'interface peptides'. 878 7

X-ray diffraction analysis of a human immunodeficiency virus (HIV-1) capsid (CA) protein shows that each monomer within the dimer consists of seven alpha-helices, five of which are arranged in a coiled coil-like structure. Sequence assignments were made for two of the helices, and tentative connectivity of the remainder of the protein was confirmed by the recent solution structure of a monomeric N-terminal fragment. The C-terminal third of the protein is mostly disordered in the crystal. The longest helices in the coiled coil-like structure are separated by a long, highly antigenic peptide that includes the binding site of an antibody fragment complexed with CA in the crystal. The site of binding of the Fab, the position of the antigenic loop and the site of cleavage between the matrix protein and CA establish the side of the dimer that would be on the exterior of the retroviral core.
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PMID:Crystal structure of dimeric HIV-1 capsid protein. 878 50

Identification and characterization of antigen-specific T lymphocytes during the course of an immune response is tedious and indirect. To address this problem, the peptide-major histocompatability complex (MHC) ligand for a given population of T cells was multimerized to make soluble peptide-MHC tetramers. Tetramers of human lymphocyte antigen A2 that were complexed with two different human immunodeficiency virus (HIV)-derived peptides or with a peptide derived from influenza A matrix protein bound to peptide-specific cytotoxic T cells in vitro and to T cells from the blood of HIV-infected individuals. In general, tetramer binding correlated well with cytotoxicity assays. This approach should be useful in the analysis of T cells specific for infectious agents, tumors, and autoantigens.
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PMID:Phenotypic analysis of antigen-specific T lymphocytes. 881 Feb 54

It has been postulated that human cytomegalovirus (HCMV) infection may have a role in the pathogenesis of common variable immunodeficiency (CVID). Many patients have a lymphocyte phenotype similar to that seen in HCMV infection, HCMV mononucleosis may precipitate hypogammaglobulinaemia, and a previous small study of common variable immunodeficient patients reported a high rate of active HCMV infection. This study investigated the presence and activity of HCMV infection in 102 CVID patients. Buffy coats were examined for the presence of HCMV IE and glycoprotein B genes using highly sensitive nested PCR. 30 blood donors of known HCMV serologic status were used as controls. There was no significant difference in HCMV positivity by PCR between patients and controls. Enrichment for mononuclear cells prior to PCR had no effect on sensitivity. Twenty-five patients were also examined for HCMV antigenaemia by staining buffy coat cytospins with monoclonal antibodies directed against the HCMV pp65 lower matrix protein, a technique widely used for diagnosis of active HCMV disease. Only one patient was positive (and also positive by PCR). Whilst these results do not exclude prior infection contributing to antibody deficiency in a small proportion of CVID patients, this study refutes the previously reported increase in active HCMV infection in CVID.
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PMID:Human cytomegalovirus infection is not increased in common variable immunodeficiency. 888 96

The incorporation of the envelope (env) glycoprotein of the human immunodeficiency virus type 1 (HIV-1) into budding virions has been proposed to be mediated by an interaction between its cytoplasmic domain and the matrix protein of HIV-1. However, this interaction was never directly demonstrated and its role in the biogenesis of HIV-1 virions is still debated. Here, a direct interaction is reported between the matrix protein of HIV-1 and the cytoplasmic domain of the env protein of HIV-1. No interaction was seen with the env cytoplasmic domain of other retroviruses. The region of the HIV-1 env involved in the interaction was delineated by mutagenesis and is comprised of the C-terminal 67 amino acid residues of env. These results, as well as the analysis of mutants of the matrix protein, suggest that the interaction between the HIV-1 env and matrix proteins accounts for the specific incorporation of the env glycoprotein into HIV-1 virions.
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PMID:Direct interaction between the envelope and matrix proteins of HIV-1. 891 55

A structurally highly ordered arrangement of the polyprotein precursor, Pr55gag is a necessary prerequisite for assembly, budding and maturation of the human immunodeficiency virus type 1 (HIV-1). In particular, distinct regions of the matrix protein (p17) and the capsid protein (p24) contained within Pr55gag are functionally active during these processes. In order to determine such regions we exchanged amino acid triplets within p17 (amino acids 46-61) and p24 (amino acids 341-352) for alanine residues and deleted the whole regions. Synthetic peptides derived from these regions had been shown previously to inhibit the production of infectious virus. The effect of the mutations on the release of viral particles was investigated by using recombinant baculoviruses for the expression of mutated Pr55gag as virus-like particles and by use of the respective HI proviruses for monitoring the production of infectious particles.
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PMID:Defined amino acids in the gag proteins of human immunodeficiency virus type 1 are functionally active during virus assembly. 895 67

The human immunodeficiency virus type 1 matrix protein (p17MA) plays a central role at both the early and late stages of the virus life cycle. During viral assembly, the p17MA domain of Pr55gag promotes membrane association, which is essential for the formation of viral particles. When viral infection occurs, the mature p17MA dissociates from the plasma membrane and participates in the nuclear targeting process. Thus, p17MA contains a reversible membrane binding signal to govern its differential subcellular localization and biological functions. We previously identified a membrane binding signal within the amino-terminal 31 amino acids of the matrix domain of human immunodeficiency virus type 1 Gag, consisting of myristate and a highly basic region (W. Zhou, L. J. Parent, J. W. Wills, and M. D. Resh, J. Virol. 68:2556-2569, 1994). Here we show that exposure of this membrane binding signal is regulated in different Gag protein contexts. Within full-length Pr55gag, the membrane targeting signal is exposed and can direct Pr55gag as well as heterologous proteins to the plasma membrane. However, in the context of p17MA alone, this signal is hidden and unable to confer plasma membrane binding. To investigate the molecular mechanism for regulation of membrane binding, a series of deletions within p17MA was generated by sequentially removing alpha-helical regions defined by the nuclear magnetic resonance structure. Removal of the last alpha helix (amino acids 97 to 109) of p17MA was associated with enhancement of binding to biological membranes in vitro and in vivo. Liposome binding experiments indicated that the C-terminal region of p17MA exerts a negative effect on the N-terminal MA membrane targeting domain by sequestering the myristate signal. We propose that mature p17MA adopts a conformation different from that of the p17MA domain within Pr55gag and present evidence to support this hypothesis. It is likely that such a conformational change results in an N-terminal myristyl switch which governs differential membrane binding.
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PMID:Differential membrane binding of the human immunodeficiency virus type 1 matrix protein. 897 Sep 78

In this study, we evaluated the effects of human immunodeficiency virus type 1 (HIV-1) on some morphologic and functional changes in cultured human monocytes/macrophages at different stages of differentiation. Freshly isolated monocytes infected with HIV-1 24 hours after seeding exhibited marked morphologic changes such as uropod formation, polarization of intercellular adhesion molecule-1 (ICAM-1) on the cytoplasmic projection, the redistribution of alpha-actinin on cell-membrane dots, and an increased release of soluble ICAM-1. These changes preceded the increase in monocyte-monocyte fusion and the formation of multinucleated giant cells. In contrast, HIV-1 infection did not affect monocyte-derived macrophages in terms of either cellular polarization or multinucleated giant cell formation. Immunocytochemistry showed that HIV-1 matrix protein was present mostly in bi- and trinucleated cells, which suggests that multinucleated giant cells may represent a long-lived and highly productive cellular source of HIV. The treatment of the HIV-1-infected monocytes with azidodeoxythymidine virtually abolished all viral-induced morphofunctional changes. On the whole, these results indicate that blood monocytes and differentiated macrophages may be affected differently by HIV infection, as monocytes seem to be much more prone to polarize, undergo homotypic fusion, and form multinucleated giant cells. These changes may confer to HIV-infected monocytes an increased ability to transmigrate through endothelia into tissues, whereas differentiated macrophages may have a predominant role as a widespread reservoir of HIV.
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PMID:Human immunodeficiency virus type 1 induces cellular polarization, intercellular adhesion molecule-1 redistribution, and multinucleated giant cell generation in human primary monocytes but not in monocyte-derived macrophages. 897 73

The three-dimensional solution- and solid-state structures of the human immunodeficiency virus type-1 (HIV-1) matrix protein have been determined recently in our laboratories by NMR and X-ray crystallographic methods (Massiah et al. 1994. J Mol Biol 244:198-223; Hill et al. 1996. Proc Natl Acad Sci USA 93:3099-3104). The matrix protein exists as a monomer in solution at low millimolar protein concentrations, but forms trimers in three different crystal lattices. Although the NMR and X-ray structures are similar, detailed comparisons have revealed an approximately 6 A displacement of a short 3(10) helix (Pro 66-Gly 71) located at the trimer interface. High quality electron density and nuclear Overhauser effect (NOE) data support the integrity of the X-ray and NMR models, respectively. Because matrix apparently associates with the viral membrane as a trimer, displacement of the 3(10) helix may reflect a physiologically relevant conformational change that occurs during virion assembly and disassembly. These findings further suggest that Pro 66 and Gly 71, which bracket the 3(10) helix, serve as "hinges" that allow the 3(10) helix to undergo this structural reorientation.
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PMID:Comparison of the NMR and X-ray structures of the HIV-1 matrix protein: evidence for conformational changes during viral assembly. 897 48


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