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)

The human immunodeficiency virus type 1 (HIV-1) Rev protein mediates the accumulation of unspliced and singly spliced viral transcripts within the cytoplasm of infected cells, late in the infection cycle, leading to the expression of the viral structural proteins, Gag, Pol, and Env. Rev binds to a complex RNA structure, the Rev-responsive element (RRE), present in all Rev-responsive viral transcripts, relieving their nuclear sequestration. The precise mechanism by which RRE-containing transcripts are retained within the nucleus in the absence of Rev protein is not well understood. We previously demonstrated that the RRE alone plays a crucial role in the nuclear retention of RRE-containing env transcripts in stably transfected Drosophila cells. Here we extend our previous observations and demonstrate that the RRE is a principal determinant of nuclear retention for envelope transcripts in primate cells and, in particular, human CD4+ T cells.
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PMID:The rev-responsive element negatively regulates human immunodeficiency virus type 1 env mRNA expression in primate cells. 870 94

The Gag-Pol polyprotein of human immunodeficiency virus type 1 is not required for efficient viral particle assembly or release. However, in this report we demonstrate that the synthesis of a truncated Gag-Pol precursor due to a premature termination codon in pol can reduce the ability of a full-length provirus to direct the formation of viral particles. Marked effects on particle production were seen when premature termination codons were introduced into the integrase (IN)-coding region. By contrast, a mutant which lacked both IN and reverse transcriptase (RT) formed particles with normal efficiency. Particle production by IN mutants was restored to wild-type levels when a second premature termination codon was introduced at the 5' end of the RT-coding sequence. Particle formation was similarly restored by a second site mutation in the viral protease (PR) gene which prevented proteolytic processing of the Gag polyprotein. Finally particle formation was restored in the presence of A77003, a specific inhibitor of human immunodeficiency virus type 1 PR. These results suggest that the effects of a lack of IN sequences on particle formation require the synthesis of a Gag-Pol precursor which contains RT sequences and are due to inappropriate PR activity.
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PMID:Lack of integrase can markedly affect human immunodeficiency virus type 1 particle production in the presence of an active viral protease. 879 22

Lentiviral Gag polyproteins have a proline-rich protein, p6, at their C terminus. There are conflicting reports about the function of p6 in virus release. In the present work, mutants that affect p6 of human immunodeficiency virus type 1 (HIV-1) Gag polyprotein were constructed and analysed. None of the mutants prevented virus release completely; however, detachment of budding particles was less efficient as evidenced by electron microscopy. Virions of the p6 truncation mutant B2TAA had a significantly reduced number of Pol proteins (p66, p51 and p34) and an increased amount of incompletely processed Gag proteins compared with the parental virus. A mutation that altered the cleavage site between p6 and p1 did not significantly affect virus assembly, virus release or protein processing with the exception of cleavage between p6 and p1. However, virions of this mutant (B2P6C) exhibited irregular-shaped core structures that were distinct from the cone-shaped core structure seen in the parental virion. B2P6C mutant virus was non-infectious in CD4+ T cells. These results suggest that mutations in p6 affect efficient detachment of budding particles from the cell surface. Proper cleavage between p6 and p1 may be critical for the formation of the distinctive cone-shaped core structure of HIV-1 virions.
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PMID:Role of the C terminus Gag protein in human immunodeficiency virus type 1 virion assembly and maturation. 884 26

The aspartyl proteinase (PR) encoded by the feline immunodeficiency virus (FIV) was prepared by total chemical synthesis. The 116-amino-acid polypeptide chain was assembled in a stepwise fashion using a Boc chemistry solid-phase peptide synthesis approach and subsequently folded into the biologically active dimeric proteinase. The synthetic enzyme showed proteolytic activity against a variety of different peptide substrates corresponding to putative cleavage sites of the Gag and Gag-Pol polyproteins of FIV. A comparative study with the proteinase of human immunodeficiency virus type 1 (HIV-1) showed that the FIV and HIV-1 enzymes have related but distinct substrate specificities. In particular, HIV-1 PR and FIV PR each show a strong preference for their own MA/CA substrates, despite identical amino acid residues at four of seven positions from P3-P4' of the substrate including an identical MA/CA cleavage site (between Tyr approximately Pro residues). FIV PR also showed a requirement for a longer peptide substrate than HIV-1 PR. Defining the similarities and the differences in the properties of these two retroviral enzymes will have a significant impact on structure-based drug design.
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PMID:Comparative properties of feline immunodeficiency virus (FIV) and human immunodeficiency virus type 1 (HIV-1) proteinases prepared by total chemical synthesis. 886 21

The selected part of gag gene (nucleotide sequences at position 618 to 1724) coding for P24 and P15 proteins of feline immunodeficiency virus (FIV) was expressed in vaccinia virus vector under control of 7.5 kDa vaccinia virus transtriptional signal (p 7.5 vaccinia virus early/late promoter). The vaccinia virus recombinant (denoted VV-G(1)) was generated by homologous recombination following CV-1 cells transfection with a newly prepared vaccinia virus insertion vector -- pWKr75.
Acta Microbiol Pol 1995
PMID:Expression of feline immunodeficiency virus (FIV) gag gene in vaccinia virus vector. 890 35

The Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disease, which belongs to the family of genetically determined instability syndromes and to the growing category of ataxia telangiectasia (AT)--related disorders. The main manifestations include pronounced microcephaly with mental retardation in most patients, "bird-like" facies, growth retardation, immunodeficiency, chromosome instability with multiple chromosome 7 and 14 rearrangements, hypersensitivity to ionizing radiation and normal AFP level. In light of high predisposition to malignancy, an accurate diagnosis is very important for the patient.
Pediatr Pol 1996 Mar
PMID:[Microcephaly with chromosomal instability and immunodeficiency--Nijmegen syndrome]. 896 94

The Vif protein of human immunodeficiency virus type 1 is required for productive replication in peripheral blood lymphocytes and a limited number of immortalized T-lymphoid lines (nonpermissive cells). In contrast, Vif is fully dispensable for virus replication in other T-cell lines (permissive cells). Because the infection phenotype of released virions is determined by producer cells and by the presence of Vif in those cells, we have analyzed the protein contents of purified viral particles in an attempt to define compositional differences that could explain the infection phenotype. Surprisingly, we were unable to discern any Vif- or cell-type-dependent quantitative or qualitative difference in the Gag, Pol, and Env proteins of virions or virus-producing cells that correlates with virus infectivity. We were, however, able to demonstrate that Vif itself is present in virions and, using semiquantitative Western blotting (immunoblotting), that there is an average of 30 to 80 molecules of Vif incorporated into each virion. Importantly, parallel analyses of total lysates of the producer cells revealed that the cell-associated expression levels of Vif are close to those of the Gag proteins. Given the dramatically higher abundance of Vif in cells than in virions, we speculate that Vif exerts its principal activity during the processes of virus assembly and budding and that this function could be of a structural-conformational nature.
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PMID:Human immunodeficiency virus type 1 Vif does not influence expression or virion incorporation of gag-, pol-, and env-encoded proteins. 897 Sep 45

We have determined the crystal structure of dUTP pyrophosphatase (dUTPase) from feline immunodeficiency virus (FIV) at 1.9 A resolution. The structure has been solved by the multiple isomorphous replacement (MIR) method using a P6(3) crystal form. The results show that the enzyme is a trimer of 14.3 kDa subunits with marked structural similarity to E. coli dUTPase. In both enzymes the C-terminal strand of an anti-parallel beta-barrel participates in the beta-sheet of an adjacent subunit to form an interdigitated, biologically functional trimer. In the P6(3) crystal form one trimer packs on the 6(3) screw-axis and another on the threefold axis so that there are two independent monomers per asymmetric unit. A Mg2+ ion is coordinated by three asparate residues on the threefold axis of each trimer. Alignment of 17 viral, prokaryotic, and eukaryotic dUTPase sequences reveals five conserved motifs. Four of these map onto the interface between pairs of subunits, defining a putative active site region; the fifth resides in the C-terminal 16 residues, which is disordered in the crystals. Conserved motifs from all three subunits are required to create a given active site. With respect to viral protein expression, it is particularly interesting that the gene for dUTPase (DU) resides in the middle of the Pol gene, the enzyme cassette of the retroviral genome. Other enzymes encoded in the Pol polyprotein, including protease (PR), reverse transcriptase (RT), and most likely integrase (IN), are dimeric enzymes, which implies that the stoichiometry of expression of active trimeric dUTPase is distinct from the other Pol-encoded enzymes. Additionally, due to structural constraints, it is unlikely that dUTPase can attain an active form prior to cleavage from the polyprotein.
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PMID:Crystal structure of dUTP pyrophosphatase from feline immunodeficiency virus. 897 51

Although very little is known about the aetiology of sarcoidosis, its immunopathogenesis is now better known. The interaction of alveolar macrophages and T cells may play a role in the pathomechanism of the disease. To infiltrate the tissue, lymphocytes have to migrate through the subendothelial basement membrane and interstitium, rich in extracellular matrix (ECM). The interaction of lymphocytes with proteins of the ECM may play an important role in the migration, accumulation and activation of these cells. The aim of our study was to estimate the ability of the ECM components (collagen I, collagen IV and fibronectin) to co-stimulate T-cells in patients with sarcoidosis. The peripheral blood was obtained from 14 sarcoid patients. The disease was confirmed histologically in 9 cases and in 5 patients on clinical grounds. In radiological findings 4 persons were at the first stage of the disease, 4 at the second, in three cases interstitial changes were found and in three patients, the fibrosis on the X-ray was noticed. No one of those patients were treated with steroids during last 2 months. Normal peripheral blood T cells are strongly co-stimulated by ECM proteins. In contrast, lymphocytes from patients with sarcoidosis were inhibited by the ECM proteins. The mean co-stimulation ratios (OKT3 + ECM proteins:OKT3 alone) were significantly lower for all ECM proteins (collagen I: p < 0.00009; collagen IV: p < 0.02; fibronectin: p < 0.04). Our data shed a new light on the nature of sarcoidosis associated immunodeficiency and suggest that disturbed T cells: ECM interactions may play a role in the pathogenesis.
Pneumonol Alergol Pol 1996
PMID:[Co-stimulating effect of extracellular matrix proteins on T lymphocyte proliferation in patients with sarcoidosis. Preliminary tests]. 899 64

Highly conserved amino acids in the second helix structure of the human immunodeficiency virus type 1 (HIV-1) MA protein were identified to be critical for the incorporation of viral Env proteins into HIV-1 virions from transfected COS-7 cells. The effects of these MA mutations on viral replication in the HIV-1 natural target cells, CD4+ T lymphocytes, were evaluated by using a newly developed system. In CD4+ T lymphocytes, mutations in the MA domain of HIV-1 Gag also inhibited the incorporation of viral Env proteins into mature HIV-1 virions. Furthermore, mutations in the MA domain of HIV-1 Gag reduced surface expression of viral Env proteins in CD4+ T lymphocytes. The synthesis of gp160 and cleavage of gp160 to gp120 were not significantly affected by MA mutations. On the other hand, the stability of gp120 in MA mutant-infected cells was significantly reduced compared to that in the parental wild-type virus-infected cells. These results suggest that functional interaction between HIV-1 Gag and Env proteins is not only critical for efficient incorporation of Env proteins into mature virions but also important for proper intracellular transport and stable surface expression of viral Env proteins in infected CD4+ T lymphocytes. A single amino acid substitution in MA abolished virus infectivity in dividing CD4+ T lymphocytes without significantly affecting virus assembly, virus release, or incorporation of Gag-Pol and Env proteins, suggesting that in addition to its functional role in virus assembly, the MA protein of HIV-1 also plays an important role in other steps of virus replication.
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PMID:Mutations in the matrix protein of human immunodeficiency virus type 1 inhibit surface expression and virion incorporation of viral envelope glycoproteins in CD4+ T lymphocytes. 899 70


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