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 envelope glycoprotein of human immunodeficiency virus (HIV) initiates infection by mediating fusion of the viral envelope with the cell membrane. Fusion activity requires proteolytic cleavage of the gp160 protein into gp120 and gp41 at a site containing several arginine and lysine residues. Activation at basic cleavage sites is observed with many membrane proteins of cellular and viral origin. We have recently found that the enzyme activating the haemagglutinin of fowl plague virus (FPV), an avian influenza virus, is furin. Furin, a subtilisin-like eukaryotic endoprotease, has a substrate specificity for the consensus amino-acid sequence Arg-X-Lys/Arg-Arg at the cleavage site. We show here that the glycoprotein of HIV-1, which has the same protease recognition motif as the FPV haemagglutinin, is also activated by furin.
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PMID:Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160. 136 Jan 48

Previously described FVB/N mice harboring a human immunodeficiency virus (HIV) long terminal repeat (LTR)/chloramphenicol acetyl transferase (CAT) transgene were treated with varying amounts of 254 nm UV-C radiation or 312 nm UV-B radiation. At optimal exposure periods, a 20-fold increase in HIV-LTR-directed expression was observed in ear specimens collected 24 h following UV-C exposure; a fourfold increase in expression was induced by UV-B exposure. Investigation of the kinetics of UV-C induction in vivo revealed that LTR-directed gene expression began to increase 2 hours after exposure and reached a maximum on Day 3 following exposure (greater than 30-fold induction). In experiments examining the kinetics of UV-B activation, the maximum level of CAT activity in the ears of irradiated transgenic animals was fivefold above levels in unirradiated transgenic controls (Day 5). Furthermore, CAT activity was not induced in fur-bearing skin following UV exposure; however, a fourfold increase in HIV-LTR-directed expression could be elicited when hair was removed by shaving prior to UV-B treatment.
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PMID:Ultraviolet radiation increases HIV-long terminal repeat-directed expression in transgenic mice. 174 79

Scurfy (sf) is a spontaneous, sex-linked, recessive mutation that maps to the extreme proximal portion of the X chromosome, about 2 centimorgans from sparse fur (spf). Hemizygotes for sf manifest several clinical disorders, evident at 14 days of age, including scaliness and crusting of the eyelids, ears, and tail, runting, reddening and swelling of the genital papilla, anemia, cachexia, and early death (average, 24 days). Our studies indicate that the phenotype of hemizygous scurfy is not, as has been suggested, a model for human X-linked ichthyosis, but appears to be a disease primarily affecting the lymphoreticular, and possibly the hematopoietic, systems. Gross lesions include marked splenomegaly, hepatomegaly, enlarged lymph nodes, and variable thickening of the ears. The characteristic histologic lesion is a lymphohistiocytic proliferation and infiltration of peripheral lymph nodes, spleen, liver, and skin. In routine hematoxylin and eosin-stained sections, these lesions efface lymph node architecture, thicken the dermis, and form nodular portal infiltrates in the liver. Scurfy lesions characteristically contain a population of large blastlike cells with round to oval nuclei, a vesicular chromatin pattern, and prominent single nucleoli. Mixed perivascular infiltrates of lymphocytes, macrophages, and granulocytes sometimes are found in kidney, heart, pancreas, lung, and mesenteries. There is excessive hematopoiesis in the liver and spleen. Cells expressing B220 or Thy-1 antigens localize to appropriate areas in the lymph nodes and spleen, but are rare in the portal infiltrates and are absent from the skin. There is a marked, polyclonal increase in serum IgG, severe Coombs'-positive anemia, and leukocytosis with atypical mononuclear cells. Scurfy mice are negative for antinuclear antibodies. Despite their morphologically aberrant lymphoreticular system, scurfy mice can exist in a conventional environment without evidence of opportunistic infection. Raising scurfy mice in a specific-pathogen-free environment does not alter disease expression. Thus, while our findings indicate that scurfy disease may be the result of immune dysfunction, it is not a classic immunodeficiency.
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PMID:X-linked lymphoreticular disease in the scurfy (sf) mutant mouse. 205 95

Twenty-six 8-year-old children who had had respiratory syncytial virus (RSV) bronchiolitis in infancy and their paired controls underwent skin and blood tests to assess the role of immunodeficiency and atopy in the pathogenesis of RSV bronchiolitis and the wheezing that may follow it. There was no difference between patients and controls in prevalence of atopy; positive results of prick tests to common antigens; eosinophil counts; yeast opsonisation defect; C2 deficiency; IgG, IgA, IgM, and IgE concentrations; or IgE antibody to dermatophagoides, timothy-grass pollen, and cat fur. Those of the children who had had RSV bronchiolitis and who continued to wheeze had a slightly higher mean eosinophil count and levels of IgE antibody to dermatophagoides than those who did not wheeze. Exercise-induced bronchial lability, though higher in patients than controls, did not correlate significantly with eosinophil counts or IgE concentrations. The genetic factors predisposing to RSV bronchiolitis and postbronchiolitic wheezing may differ from those predisposing to atopic asthma, though exclusive breast feeding may protect against both.
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PMID:Atopy does not predispose to RSV bronchiolitis or postbronchiolitic wheezing. 678 13

A small 14 amino acid oligopeptide tag (termed SV5-Pk) was fused onto the carboxy-terminus of simian immunodeficiency virus gp160 expressed from a recombinant baculovirus. The presence of the Pk tag had no obvious effect on the expression and glycosylation of gp160 and did not interfere either with CD4 binding or with cleavage at its maturation site by the protease furin. The presence of the Pk tag did, however, facilitate the simplified purification of full-length gp160 and its incorporation into immunogenic solid matrix-antibody-antigen (SMAA) complexes.
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PMID:Attachment of an oligopeptide epitope to the C-terminus of recombinant SIV gp160 facilitates the construction of SMAA complexes while preserving CD4 binding. 754 87

A key event in the biosynthesis of the human immunodeficiency virus is the maturation of the gp160 precursor generating gp120 and gp41, two proteins that are fundamental for the infective process. In vivo, gp160 is specifically cleaved at the 515-519 site (REKR decreases A), in spite of the presence in its sequence of another consensus sequence KAKR decreases R (residues 507-511). Comparative kinetic studies on synthetic peptides reproducing different sequences of gp160 by the enzymes PC1 and furin are reported in this paper. The data demonstrate the higher efficiency of furin in the cleavage of peptidic substrates with respect to PC1 and its preference for REKR decreases A vs. KAKR decreases R. Furthermore, furin and PC1 are unable to process peptides patterned on the sequence 307-330 of specific viral strains of the gp120 V3 loop.
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PMID:Structural investigation and kinetic characterization of potential cleavage sites of HIV GP160 by human furin and PC1. 763 57

The role of the glycans of the human immunodeficiency virus type 1 transmembrane glycoprotein (gp41) in the intracellular events of Env precursor (gp160) biosynthesis has been examined by the use of a mutant gp160 in which the cluster of conserved glycosylation sites within the gp41 domain (Asn-621, -630 and -642) has been mutated. Expression of the wild-type and mutant forms of gp160 in BHK-21 cells using recombinant vaccinia viruses has shown that the kinetics of the events occurring in the endoplasmic reticulum (ER) were normal: both Env proteins had similar kinetics of disulphide bond formation, as determined by the acquisition of CD4-binding capability, and both had similar kinetics of oligomer formation. However, in contrast to the parental molecule, mutated gp160 displayed relatively slow transport from the cis to the medial Golgi where it was retained in the oligomeric state. Transport to the trans Golgi was impaired, as determined by the sensitivity of gp160 to glycosidases. Cleavage of mutated gp160 at the gp120/gp41 junction was substantially reduced but this was apparently not due to the involvement of the gp41 glycosylation in the cleavage reaction by furin inasmuch as, in the baculovirus system, mutated gp160 could be cleaved when recombinant furin was co-expressed. The reduced cleavage in mammalian cells may thus reflect the impaired routing of mutated Env to the compartment where cleavage occurs. The glycan component of gp41 is, therefore, important for the efficient intracellular transport and processing of gp160. gp160 lacking gp41 carbohydrates is an additional example, among few others, of a protein lacking glycans that is arrested in the Golgi rather than the ER following its biosynthesis.
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PMID:The glycosylation of human immunodeficiency virus type 1 transmembrane glycoprotein (gp41) is important for the efficient intracellular transport of the envelope precursor gp160. 778 80

The spike glycoproteins of many enveloped viruses are proteolytically cleaved at the carboxytermini of sequences containing the basic motif R-X-K/R-R. Cleavage is often necessary for the fusion capacity of the glycoproteins and, thus, for virus infectivity. Among these viruses are pathogenic avian influenza viruses, human parainfluenza virus, human cytomegalovirus, and human immunodeficiency virus; it has been demonstrated that these viruses can be activated by furin. Indigenous furin has been identified in T-lymphocytes, which are host cells for HIV. Furin has been localized in the TGN and on the surface of cells after vectorial expression. Peptidylchloroalkylketones have been designed that inhibit with high specificity cleavage and fusion activity of viral glycoproteins, as well as virus replication.
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PMID:Processing of viral glycoproteins by the subtilisin-like endoprotease furin and its inhibition by specific peptidylchloroalkylketones. 781 26

Intracellular proteolytic processing of human immunodeficiency virus envelope glycoprotein precursor (gp160) is an essential step for virus infectivity. Northern blot analysis provided evidence that furin and PC1, but not PC2, are expressed in the CD4+ human lymphoblastoid H9 cell line, suggesting the possible participation of these convertases in human immunodeficiency virus (HIV) gp160 proteolytic processing. Purified PC1 and furin cleaved specifically in vitro gp160 into gp120 (HIV-I SU) and gp41 (HIV-I TM). NH2-terminal sequence analysis of the produced gp41 (HIV-I TM) demonstrated that the cleavage occurred within the sequence Arg-Glu-Lys-Arg decreases Ala-Val-Gly-Ile, which is identical to the bond cleaved in vivo. Transition state analog peptides were designed and tested in vitro for their ability to inhibit the PC1- or furin-mediated gp160 cleavage. The best inhibitor was decanoyl-Arg-Lys-Arg-Arg-psi [CH2NH]-Phe-Leu-Gly-Phe-NH2.
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PMID:The convertases furin and PC1 can both cleave the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp160 into gp120 (HIV-1 SU) and gp41 (HIV-I TM). 816 29

Infection with human immunodeficiency virus type 1 (HIV-1) is associated with a high incidence of lymphoma. Typically, the lymphomas are B-cell in origin, and although they occur in the setting of HIV-1 infection, historical studies have found no evidence for the presence of HIV-1 within the transformed B-cells. We describe a new class of large cell lymphoma wherein HIV p24 expression within the tumor specimens was found to be extremely high. In the first case, HIV was expressed in the tumor-associated transformed T-cells. In three other cases, HIV was found to be highly expressed in tumor-associated macrophages. These tumors exhibited a mixed immunophenotype histologically. Analysis by inverse polymerase chain reaction, using HIV long terminal repeat primers, demonstrated monoclonal HIV integration sites for all four tumors. Direct sequencing of the T-cell lymphoma inverse polymerase chain reaction products identified the HIV integration site within the fur gene, just upstream from the c-fes/fps protooncogene. Using segments of the fur gene as a probe, the other three monoclonal integration sites mapped to the same region. Although the integration and up-regulation of c-fes/fps was localized to the tumor cells within the T-cell lymphoma, the cells containing the monoclonal HIV in the other mixed immunophenotype lymphomas are currently unknown. These observations suggest that HIV may contribute directly to lymphomagenesis and identify a common site of HIV integration within a subset of acquired immunodeficiency syndrome lymphoma.
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PMID:Identification of a common clonal human immunodeficiency virus integration site in human immunodeficiency virus-associated lymphomas. 817 6


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