Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

B- and T-cell epitopes from three distinct regions of the hepatitis B virus (HBV) envelope (env) protein (preS1, preS2 and S) are involved in eliciting protective immunity. Since preS1 sequences inhibit the secretion of HBV env proteins from eukaryotic cells, it is difficult to prepare immunogens rich in preS1 sequences. This problem can be overcome by linking synthetic peptides from the preS1 region to particles containing both S and preS2 sequences. We describe here a novel approach for binding of synthetic peptides to exposed hydrophobic domains on HBV env proteins. Long chain fatty acids or mercaptans are covalently linked to synthetic peptides. Peptides with the attached hydrophobic tails interact strongly with HBV env proteins (S + preS2), whereby hybrid immunogens are generated. Such immunogens can be used in combination with alum, the only adjuvant approved for human use. The combination of the preS1 peptide [preS(12-47)] with particles containing the S and preS2 regions resulted in an immunogen which: (1) elicits a broad spectrum of protective antibodies; (2) circumvents the nonresponsiveness to: (a) preS1 epitopes in preS1-nonresponder strains of mice; and (b) S-protein in S-protein-nonresponder strains of mice; and (3) augments the immune response to S-protein. The combination of HBV env proteins with a synthetic peptide from the envelope of the human immunodeficiency virus (HIV-1) resulted in an immunogen eliciting anti-HIV-1. Hybrid immunogens consisting of viral proteins and of synthetic peptides represent a feasible approach for the design of future vaccines.
 ...
PMID:Hepatitis B virus surface antigen (HBsAg) as carrier for synthetic peptides having an attached hydrophobic tail. 246 97

A homology has been found between an octapeptide involved in attachment of the human immunodeficiency virus to helper/inducer T cells and an octapeptide segment of bovine pancreatic ribonuclease A. This segment (residues 19-26) contains the sites for subtilisin cleavage of this enzyme into the S-peptide and S-protein. From the X-ray crystal structure of ribonuclease, this sequence is known to be exposed to solvent and interacts little with the rest of the protein. A structure for the human immunodeficiency virus attachment peptide can be deduced from this homology, as a well-defined structure has been determined for this sequence in ribonuclease. This can be readily accomplished using previously developed computer methods based upon conformational energy calculations. The calculated structure for human immunodeficiency virus peptide is identical to the ribonuclease segment (19-26) in backbone conformation. It is stabilized by internal interactions of nonpolar residues, and by exposure of polar hydroxyl groups. The results suggest that the T-cell human immunodeficiency virus receptor may be hydrophilic in nature and that conservation of the sequence in two presumably functionally unrelated proteins is related to the need for conservation of exposed structure.
 ...
PMID:A strong homology exists between the active T-cell binding gp120 octapeptide of human immunodeficiency virus and the subtilisin cleavage peptide of bovine ribonuclease A. 303 Mar 17

Recombinant human immunodeficiency virus (HIV-1) Tat protein added to the culture medium of rat cerebellar neurons promoted aggregation and formation of spoke-like neurites in a dose-dependent manner. Tat proteins containing mutations in the Arg-Gly-Asp (RGD) cell adhesion motif or a deletion of the cysteine-rich domain had no effect on neuronal morphology. In contrast, a Tat protein that contained a deletion of the proline-rich domain promoted neuronal aggregation. Aggregation of neurons was inhibited by the addition of monoclonal antibodies directed against the RGD and basic domains of Tat, but not against the proline-rich domain. The same domains of Tat required to induce aggregation also mediated adhesion of neurons to Tat-coated substrates. The HIV-2 Tat protein, which lacks an RGD sequence but contains cysteine-rich and basic domains similar to HIV-1 Tat, induced aggregation and acted as a substrate for adhesion when added at higher concentrations than HIV-1 Tat. Vitronectin, fibronectin, and RGD-containing peptides did not induce morphological changes in neurons or act as substrates for adhesion. The ability of Tat to induce morphological changes and promote adhesion was independent of the ability of Tat to transactivate HIV gene expression. Our results suggest that extracellular Tat protein most likely alters neuronal morphology and mediates adhesion by acting in a manner similar to an extracellular matrix protein.
 ...
PMID:Extracellular human immunodeficiency virus type 1 Tat protein promotes aggregation and adhesion of cerebellar neurons. 878 30

Pneumocystis carinii pneumonia remains a serious complication of immunodeficiency. Vitronectin (VN) and fibronectin (FN) accumulate in the lung during P. carinii infection and bind to the organism, thereby enhancing macrophage release of TNF alpha. It is not known whether VN and FN also regulate uptake and degradation of P. carinii by macrophage when present in concentrations similar to those in the lung during pneumonia. To address this, macrophages were cultured with 35S-radiolabeled P. carinii and organism binding, phagocytosis, and degradation determined in media alone (control), or in the presence of VN or FN (100 micrograms/ml each). Soluble VN and FN, in concentrations similar to those in the host, did not significantly affect binding uptake or degradation of P. carinii by alveolar macrophages. Thus, although VN and FN enhance macrophage activation during P. carinii pneumonia, phagocytosis of the organism is not increased by these host glycoproteins under steady-state conditions.
 ...
PMID:Steady-state effects of vitronectin and fibronectin on the binding, uptake, and degradation of Pneumocystis carinii in rat alveolar macrophages. 924 75

In vitro experiments indicate that components of the host present in body fluids may prevent the attachment of human immunodeficiency virus type 1 (HIV-1) to target cells. Fibronectin (Fn), a dimeric 440-kDa extracellular matrix adhesion protein, is secreted by mesenchymal cells and assembled into insoluble matrices. Fn exerts important effects on cell growth and differentiation through a number of discrete functional domains. Several microorganisms are known to bind Fn. We show that, under physiological conditions, HIV-1 gp120 and gp160 are capable of binding plasma and cellular Fn as well as laminin and vitronectin. Experiments were set up to analyze in detail the binding of HIV gp120 and gp160 to Fn. The gp120 and gp160 specifically recognize the C-terminal heparin-binding domain of Fn (Fn-CTHBD) with a calculated KD of 2.8 x 10(-7) M for gp160. Binding of gp160 to Fn-CTHBD is a saturable and specific process that is blocked by antibodies to Fn-CTHBD and by heparin and is inhibited to a minor extent by heparan sulfate and dextran sulfate. These observations suggest that gp120/160 specifically recognize the III15 repeat within Fn-CTHBD. Intact Fn and Fn-CTHBD strongly inhibit the interaction of gp120/160 with soluble CD4 and, under low serum conditions, are capable of neutralizing the infectivity of HIV-1 for CD4-positive T cells. Thus, Fn that is present in plasma and mucinous secretions may well affect HIV infectivity and virus distribution in vivo.
 ...
PMID:Heparin-binding domain of human fibronectin binds HIV-1 gp120/160 and reduces virus infectivity. 944 8

Kaposi's sarcoma (KS) spindle cell growth and spread have been reported to be modulated by various cytokines as well as the human immunodeficiency virus (HIV) gene product Tat. Recently, HIV-1 Tat has been shown to act like a cytokine and bind to the Flk-1/KDR receptor for the vascular endothelial growth factor A (VEGF-A), which is expressed by KS cells. We have characterized signal transduction pathways stimulated by HIV-1 Tat upon its binding to surface receptors on KS cells. We observed that stimulation in KS 38 spindle cells resulted in tyrosine phosphorylation and activation of the Flk-1/KDR receptor. We also report that HIV-1 Tat treatment enhanced the phosphorylation and association of proteins found in focal adhesions, such as the related adhesion focal tyrosine kinase RAFTK, paxillin, and p130(cas). Further characterization revealed the activation of mitogen-activated protein kinase, c-Jun amino-terminal kinase (JNK), and Src kinase. HIV-1 Tat contains a basic domain which can interact with growth factor tyrosine kinase receptors and a classical RGD sequence which may bind to and activate the surface integrin receptors for fibronectin and vitronectin. We observed that stimulation of KS cells with basic as well as RGD sequence-containing Tat peptides resulted in enhanced phosphorylation of RAFTK and activation of MAP kinase. These studies reveal that Tat stimulation activates a number of signal transduction pathways that are associated with cell growth and migration.
 ...
PMID:Human immunodeficiency virus tat modulates the Flk-1/KDR receptor, mitogen-activated protein kinases, and components of focal adhesion in Kaposi's sarcoma cells. 962 Oct 77

People infected with human immunodeficiency virus type-I (HIV-I) have an increased incidence of Kaposi's sarcoma (KS) and HIV-I infection alters the natural history of KS. The potent trans-activator HIV-I protein Tat plays a major role in the pathogenesis of acquired immunodeficiency syndrome (AIDS)-related KS. Among many of its KS-promoting activities, the Tat protein augments the angiogenic activities of basic fibroblast growth factor (bFGF), interferon gamma, and vascular endothelial growth factor (VEGF); it also mimics the effects of the extramedullary matrix proteins fibronectin and vitronectin, and increases the expression of matrix metalloproteinases. Inflammatory cytokines induce endothelial cells to acquire the phenotype and functional features of AIDS-related KS spindle cells. These cytokines act by both autocrine and paracrine mechanisms. The synergy between cytokines and the HIV-I Tat protein provides possible insight into why AIDS-related KS is more aggressive than the classic Mediterranean form, in which the HIV-I Tat protein does not play a role.
 ...
PMID:The role of human immunodeficiency virus-I in the pathogenesis of acquired immunodeficiency syndrome-related Kaposi's sarcoma: the importance of an inflammatory and angiogenic milieu. 1095 Mar 68

RNase S is a unique protein comprising the non-covalent association of two components, the S-peptide and the S-protein. An RNA-recognition segment derived from the human immunodeficiency virus (HIV)-1 Rev protein was conjugated with the S-peptide to form a complex with the S-protein. The resulting RNase S bearing the RNA-recognition segment preferentially hydrolyzed a single position of the RNA stem-loop derived from the specific binding site for the Rev protein.
 ...
PMID:A 'cassette' RNase: site-selective cleavage of RNA by RNase S equipped with RNA-recognition segment. 1135 68

Infection of receptor-bearing cells by coronaviruses is mediated by their spike (S) proteins. The coronavirus (SARS-CoV) that causes severe acute respiratory syndrome (SARS) infects cells expressing the receptor angiotensin-converting enzyme 2 (ACE2). Here we show that codon optimization of the SARS-CoV S-protein gene substantially enhanced S-protein expression. We also found that two retroviruses, simian immunodeficiency virus (SIV) and murine leukemia virus, both expressing green fluorescent protein and pseudotyped with SARS-CoV S protein or S-protein variants, efficiently infected HEK293T cells stably expressing ACE2. Infection mediated by an S-protein variant whose cytoplasmic domain had been truncated and altered to include a fragment of the cytoplasmic tail of the human immunodeficiency virus type 1 envelope glycoprotein was, in both cases, substantially more efficient than that mediated by wild-type S protein. Using S-protein-pseudotyped SIV, we found that the enzymatic activity of ACE2 made no contribution to S-protein-mediated infection. Finally, we show that a soluble and catalytically inactive form of ACE2 potently blocked infection by S-protein-pseudotyped retrovirus and by SARS-CoV. These results permit studies of SARS-CoV entry inhibitors without the use of live virus and suggest a candidate therapy for SARS.
 ...
PMID:Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2. 1536 30

Lentiviral replication in its target cells affects a delicate balance between cellular cofactors required for virus propagation and immunoregulation for host defense. To better elucidate cellular proteins linked to viral infection, we tested plasma from rhesus macaques infected with the simian immunodeficiency viral strain SIVsmm9, prior to, 10 days (acute), and 49 weeks (chronic) after viral infection. Changes in plasma protein content were measured by quantitative mass spectrometry by isobaric tags for absolute and relative quantitation (iTRAQ) methods. An 81 and 232% increase in SERPINA1 was seen during acute and chronic infection, respectively. Interestingly, gelsolin, vitamin D binding protein and histidine rich glycoprotein were decreased by 45% in acute conditions but returned to baseline during chronic infection. When compared to uninfected controls, a 48-103% increase in leucine rich alpha 2-glycoprotein, vitronectin, and ceruloplasmin was observed during chronic viral infection. Observed changes in plasma proteins expression likely represent a compensatory host response to persistent viral infection.
 ...
PMID:Plasma proteomic analysis of simian immunodeficiency virus infection of rhesus macaques. 2067 26


1 2 Next >>