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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many unexpected biological functions as bioreactants of the intracellular proteases and their endogenous inhibitors have been found recently. Chymase and tryptase in histamine granules of mast cells and basophile cells play an important role in the process of IgE-mediated degranulation and in the formation of an allergic inflammation profile. Furthermore, the relationship between membrane proteases and their endogenous inhibitor has been taken up as a key and key-hole relation which plays an important role for special recognition apparatus of biological information like the relation of peptide hormones (growth factors) and their specific receptors. Amino acid sequences of the active site of trypstatin are homologous with the neutralizing epitope beta of gp120 of AIDS virus (HIV-1). The trypstatin and anti-tryptase M antibody inhibited syncytium formation in HIV infected Molt 4, clone 8 cells. Therefore, the relationship between tryptase M with trypstatin and the recognition site of epitope beta of HIV-1 with the receptor of helper T-cells are the common keys. The precursor of Alzheimer's deposition protein contains a Kunitz-type trypsin inhibitor domain. The A4-precursor proteins are located in axons of pyramidal neurons in brain and secretory granules of chromaffin cells in adrenal medulla. Those may be secreted into the extracellular milieu. We propose that the A4 inhibitor inhibits a special type of tryptase in the brain and disturbs the complete degradation of secreted A4-precursor protein causing amyloid deposition in alzheimer disease by abnormal proteolysis. Human c-Ha-ras p21 shows 58% homology with cystatin beta, an endogenous inhibitor of cathepsin. Actually, p21 inhibits cathepsin L specifically, but not cathepsin H, papain and cathepsin B. However, the metabolic significance of this inhibitory activity is still unknown.
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PMID:New biological functions of intracellular proteases and their endogenous inhibitors as bioreactants. 220 23

Twenty eight patients aged 18 to 40 years with urogenital infections complicated by orchiepididymitis were examined immunologically. The use of specific monoclonal antibodies OKT-4+ and OKT-8 revealed lower contents of T-helper cells (Thc) (23.33 +/- 9.7%) and higher contents of T-suppressor cells (Tsc) (41.17 +/- 13.41%) in them as compared to those in healthy volunteers (18 persons) and patients with noncomplicated urogenital infections (19 persons). There was a significant decrease in the immunoregulatory index (IRI): Thc/Tsc (0.68 +/- 0.33) reached in some patients the ratio observed in persons infected with the HIV (0.6 +/- 0.2) and an increase in the contents of circulating immune complexes (CIC) (28.5 +/- 2.0 arbitrary units against the normal of 10.0 +/- 0.7). Enzyme therapy including the use of chymotrypsin and trypsin manufactured in the USSR in doses of 10 mg each administered intramuscularly once a day or in doses of 5 mg each administered intramuscularly twice a day for 10 days promoted normalization of the impaired immunity indices (Thc 44.0 +/- 10.51%, Tsc 31.5 +/- 11.26%, IRI 1.53 +/- 0.33 and CIC 12.1 +/- 0.74 arbitrary units). Therefore, the enzymes had an immunomodulating effect. It is likely that they will be useful in treatment of infectious inflammatory processes accompanied by analogous immune disorders which makes the enzyme immunocorrection more applicable in treatment of various pathological processes.
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PMID:[Immunologic foundation of enzyme therapy of patients with orchiepididymitis]. 228 42

Ovine lentiviruses share genome sequence, structural features, and replicative mechanisms with HIV, the etiologic agent of AIDS. A lamb model of lentivirus-induced lymphoid interstitial pneumonia, comparable to lymphoid interstitial pneumonia associated with pediatric AIDS, was used to investigate production of leukocyte-soluble mediators. Lentivirus-infected lambs and adult sheep with severe lymphoid interstitial pneumonia had significantly elevated levels of spontaneous interferon (IFN) production from pulmonary leukocytes compared with ovine lentiviruses-infected animals with mild or no lesions of lymphoid interstitial pneumonia or non-infected controls. However, peripheral blood mononuclear cells from lentivirus-infected lambs did not spontaneously release significant amounts of IFN. IFN production by pulmonary lymph node lymphocytes was enhanced in the presence of lentivirus-infected alveolar macrophages. Animals with lentivirus-induced disease and spontaneous IFN production had enhanced virus replication within tissues. The ovine lentiviruses-induced IFN had a m.w. of between 25,000 and 35,000 and was resistant to freeze/thawing procedures. The IFN activity was sensitive to trypsin and stable to low pH and heat. IFN with similar physical and biochemical properties was produced when ovine lentiviruses was added to control leukocyte cultures. IL-2 and PGE2 production and responses to mitogen by pulmonary lymph node lymphocytes of lentivirus-diseased lambs were not statistically different from control animals. Increased local production of IFN in lentivirus-infected host tissues may serve to accelerate the entry of leukocytes into virus-induced lesions promoting cell-mediated tissue damage and also provide increased numbers of cells for virus replication.
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PMID:Spontaneous interferon production by pulmonary leukocytes is associated with lentivirus-induced lymphoid interstitial pneumonia. 244 76

Bacterially expressed recombinant HIV-1 reverse transcriptase is active as both a homodimer of Mr 66,000 subunits and a heterodimer of Mr 66,000 and 51,000 subunits. The heterodimer is formed by cleavage of a C-terminal fragment from one Mr 66,000 polypeptide, which occurs during purification and crystallization of reverse transcriptase. Thus, crystals obtained from purified Mr 66,000 polypeptide preparations consisted of an apparently equimolar mixture of Mr 66,000 and 51,000 polypeptides, which were apparently analogous to the Mr 66,000 and 51,000 polypeptides detected in HIV-infected cells and in virions. Limited proteolysis of the homodimer with alpha-chymotrypsin also resulted in cleavage to a stable Mr 66,000/51,000 mixture, and proteolysis with trypsin resulted in the transient formation of some Mr 51,000 polypeptide. These results are consistent with the reverse transcriptase molecule having a protease-sensitive linker region following a structured domain of Mr 51,000. Further digestion with trypsin resulted in cleavage of the Mr 51,000 polypeptide after residue 223, yielding peptides of apparent Mr 29,000 and 30,000. A minor peptide of Mr 40,000 was also produced by cleavage of the Mr 66,000 polypeptide after residue 223. About half the original Mr 66,000 polypeptides remained resistant to proteolysis and existed in complex with the above peptides in solution. During both chymotrypsin and trypsin digestion there was an increase in the reverse transcriptase activity caused by a doubling of Vmax with little change in Km for dTTP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HIV-1 reverse transcriptase: crystallization and analysis of domain structure by limited proteolysis. 246 81

Trypstatin, a new cellular Kunitz-type protease inhibitor purified from rat mast cells, inhibited syncytium formation in human immunodeficiency virus type 1 (HIV-1)-infected CCRF-CEM and uninfected Molt-4 clone 8 at a concentration of 1 microM. Anti-rat tongue mast cell tryptase antibodies reacted with Molt-4 clone 8 cells, as determined by Western blot and by immunofluorescence. In addition, the antibody inhibited syncytium formation. These findings along with homologous sequences with trypstatin and a neutralizing epitope of gp120 of HIV-1 suggest that a tryptase-like cellular enzyme(s) is involved in HIV-1 infection.
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PMID:Involvement of tryptase-related cellular protease(s) in human immunodeficiency virus type 1 infection. 247 Jun 18

A neutralizing epitope (epitope beta) of the HTLV-IIIB strain of HIV-1 was mapped to 24 amino acids of an external envelope glycoprotein (gp120) using a neutralizing monoclonal antibody (0.5 beta) and hetero-antisera against synthetic peptides encoding gp120. Proteins that have homologous sequences with epitope beta were sought from a databank of protein sequences to assess biological features of epitope beta. The results showed that epitope beta was found to have homologous sequences to inter-alpha-trypsin inhibitor (ITI). The homologous region of ITI included the active site of the protein. Synthesized peptides including epitope beta were good substrates for trypsin, because these peptides inhibited trypsin activities in a competitive manner (Ki = 24.5 microM). Human urinary trypsin inhibitor (UTI), a protein indistinguishable from ITI, as well as synthetic peptides including epitope beta inhibited syncytium formation caused by the LAV-1-infected CCRF-CEM and uninfected Molt-4 cells in a dose-dependent manner (0.1-1 mM). These findings suggest that epitope beta of HIV-1 could be substrate of protease upon HIV-1 infection and also suggest that protease inhibitory activity of epitope beta may play a role in the pathophysiology of HIV-1-infected individuals.
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PMID:A neutralizing epitope of human immunodeficiency virus type 1 has homologous amino acid sequences with the active site of inter-alpha-trypsin inhibitor. 248 64

A soluble form of the human CD4 glycoprotein (sCD4), the cellular receptor for human HIV, was treated with various physical, chemical, and enzymic regimens and tested over a range of concentrations for its capacity to inhibit the binding of HIV to CD4+ T cells. Reduction of disulfide bonds and alkylation in denaturing buffer (8 M urea) destroyed the inhibitory activity of sCD4, whereas reduction and alkylation in PBS had no effect. Derivatization or digestion of carbohydrate groups by periodate oxidation or by glycolytic enzyme digestion did not affect sCD4 inhibitory capacity. Digestion with trypsin or endoproteinase Glu-C destroyed activity. A limited digestion of sCD4 with endoproteinase Glu-C resulted in a mixture of fragments, however, and the mixture had inhibitory activity equivalent to that of intact sCD4. Within this mixture, a fragment of 23 kDa was identified that binds to HIV. Although sCD4 can be digested to yield fully active fragments, the requirement for intrachain disulfide bonding indicates that the minimum sized portion of CD4 that will retain full affinity for HIV will have to be formulated with a proper tertiary structure.
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PMID:Structural features of CD4 required for binding to HIV. 253 5

Langerhans cells (LC) are epidermal dendritic cells which express several surface antigens among them the CD4 antigens. We investigated the fate of HIV envelope glycoproteins (gp 120 and gp 160) incubated with healthy human trypsinized LC in suspension. After trypsin treatment only the epitope for OKT4 appeared to be resistant. In absence of antigenic sites identified by OKT4A, Leu 3a or BL4, LC fixed and internalized gp 120 or gp 160 recombinant HIV proteins. This finding support the hypothesis that there exists at the surface of LC a second molecule which may act as a HIV receptor.
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PMID:[HIV envelope proteins are bound by human epidermal Langerhans cells by a binding site which differs from the site on the CD4 molecule, and are internalized by receptor endocytosis]. 254 85

The membrane-associated structural protein, p18, of the human immunodeficiency virus (HIV-1), has been expressed in Escherichia coli. The recombinant protein was purified by cation-exchange chromatography on S Sepharose followed by cation-exchange high-performance liquid chromatography (HPLC) on Sulfoethyl Aspartamide. The isolation of 28.7 mg of recombinant p18 from 16.71 of cell culture represents an overall yield of ca. 20%. Recombinant p18 was characterized by sodium dodecyl sulphate polyacrylamide gel electrophoresis, reversed-phase HPLC, amino acid composition and amino acid sequence analysis of the N-terminus. Edman degradation of peptides generated by trypsin or Staphylococcus aureus V8 proteolytic digestion, including the C-terminus, confirmed the amino acid sequence to be that predicted from the cDNA. A C-terminally cleaved form of recombinant p18, p18LM, was separated in the cation-exchange HPLC step and was partially characterized in parallel with the intact molecule. By Western blotting it was shown that recombinant p18 in addition to the cleaved form p18LM is recognized by a monoclonal antibody which was generated against the natural protein from HIV-1.
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PMID:Isolation of recombinant partial gag gene product p18 (HIV-1Bru) from Escherichia coli. 267 78

Human immunodeficiency virus type 1 (HIV-1) encodes a Vif protein which is important for virus replication and infectivity. Vif is a cytoplasmic protein which exists in both membrane-associated and soluble forms. The membrane-associated form is an extrinsic membrane protein which is tightly associated with the cytoplasmic side of membranes. We have analyzed the mechanism of membrane targeting of Vif and its role in HIV-1 replication. Mutagenesis studies demonstrate that C-terminal basic domains are required for membrane association. Vif mutations which disrupt membrane association also inhibit HIV-1 replication, indicating that membrane localization of Vif is likely to be required for its biological activity in vivo. Membrane binding of Vif is almost completely abolished by trypsin treatment of membranes. These results demonstrate that membrane localization of Vif requires C-terminal basic domains and interaction with a membrane-associated protein(s). This interaction may serve to direct Vif to a specific cellular site, since immunofluorescence staining and plasma membrane fractionation studies show that Vif is localized predominantly to an internal cytoplasmic compartment rather than to the plasma membrane. The mechanism of membrane targeting of Vif is different in some respects from that of other extrinsic membrane proteins, such as Ras, Src, and MARCKS, which utilize a basic domain together with a lipid modification for membrane targeting. Membrane targeting of Vif is likely to play an important role in HIV-1 replication and thus may be a therapeutic target.
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PMID:Biological activity of human immunodeficiency virus type 1 Vif requires membrane targeting by C-terminal basic domains. 747 41


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