Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A principal neutralizing domain (PND) of the major envelope glycoprotein (gp120) of the HTLV-III BH10 strain of human immunodeficiency virus type 1 (HIV-1) has significant amino acid similarities to a reactive site of Kunitz-type basic proteinase inhibitors. We therefore thought that the PND may interact with cellular proteinase-like molecule(s) upon HIV-1 infection and measured the cellular proteolytic activities at the surface of intact Molt-4 clone 8 cells, which are highly susceptible to HIV-1 infection. The cells preferentially cleaved succinyl-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide, a good substrate of chymotrypsin, and the activity was strongly inhibited by N-tosyl-L-phenylalanyl chloromethyl ketone (IC50 = 11.5 microM) and chymostatin (IC50 = 4.8 microM). A synthetic peptide of 24 residues (amino acids 308-331) that correspond to the PND also inhibited the cellular proteolytic activity in a dose-dependent manner (IC50 = 79.2 microM). The inhibition was still observed at low temperature (IC50 = 42.7 microM) and even after the peptide-treated cells were washed. We therefore think that the peptide interacts with proteinase-like molecule(s) located at the surface of the cells. The synthetic peptides from four other strains of HIV-1 corresponding to the PND similarly inhibited the proteolytic activity. These results may be helpful to clarify the novel mechanism(s) for HIV-1 infection.
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PMID:A principal neutralizing domain of human immunodeficiency virus type 1 interacts with proteinase-like molecule(s) at the surface of Molt-4 clone 8 cells. 191 51

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

Persistent infection by human immunodeficiency virus (HIV-1) in the chimpanzee may be valuable for immunopathologic and potential vaccine evaluation. Two HIV strains, the tissue culture-derived human T-cell lymphotropic virus type IIIB (HTLV-IIIB) and in vivo serially passaged lymphadenopathy-associated virus type 1 (LAV-1), were injected intravenously into chimpanzees. Two animals received HTLV-IIIB as either virus-infected H9 cells or cell-free virus. A third animal received chimpanzee-passaged LAV-1. Evaluation of their sera for virus-specific serologic changes, including neutralizations, was done during a 2-year period. During this period all animals had persistently high titers of antibodies to viral core and envelope antigens. All three animals developed a progressively increasing type-specific neutralizing LAV-1 versus HTLV-IIIB antibody titer during the 2-year observation period which broadened in specificity to include HTLV-HIRF, HTLV-IIIMN, and HTLV-IIICC after 6 to 12 months. The antibody titers against both viruses were still increasing by 2 years after experimental virus inoculation. Sera from all animals were capable of neutralizing both homologously and heterologously reisolated virus from chimpanzees. A slightly more rapid type-specific neutralizing response was noted for the animal receiving HTLV-IIIB-infected cells compared with that for cell-free HTLV-IIIB. Sera from all persistently infected chimpanzees were capable of mediating group-specific antibody-mediated complement-dependent cytolysis of HIV-infected cells derived from all isolates tested. Viruses reisolated from all three animals at 20 months after inoculation revealed very similar peptide maps of their respective envelope gp120s, as determined by two-dimensional chymotrypsin oligopeptide analysis. One peptide, however, from the original HTLV-IIIB-inoculated virus was deleted in viruses from all three animals, and in addition, we noted the appearance of a new or modified peptide which was common to LAV-1 as well as to HTLV-IIIB reisolated from infected chimpanzees. It thus appears that a group-specific neutralizing antibody response as well as a group-specific cytotoxic response can develop in chimpanzees after an inoculation of a single HIV variant. This finding suggests that a common, less immunodominant determinant(s) is present on a single HIV strain which could induce group-specific antibodies during viral infection and replication. The identification of this group-specific epitope and the induction of analogous immunity may be relevant to vaccine development against human acquired immunodeficiency syndrome.
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PMID:Persistent infection of chimpanzees with human immunodeficiency virus: serological responses and properties of reisolated viruses. 244 11

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

Infection of monocyte-macrophages with human immunodeficiency virus may be central to the pathogenesis of the acquired immunodeficiency syndrome. The ability of infected macrophages to prime T cells through IL-1 production was investigated in vitro. Purified human monocytes maintained in suspension culture were infected with strain HIV-DV. Intracellular expression of virus p24 antigen increased from undetectable levels immediately after infection to 13-59% of cells by 10-14 d; infected macrophages remained viable for up to 60 d. Supernatants collected between 14 and 20 d after infection were examined in the murine thymocyte co-mitogenesis assay and demonstrated to contain a potent IL-1 inhibitor, designated contra-IL-1. Contra-IL-1 activity was present in all supernatants examined after 4 d of infection, and peaked coincident with peak p24 antigen expression. Inhibitory activity was not present in uninfected cells. Contra-IL-1 activity eluted after gel filtration with an approximate molecular weight of 9 kD. Inhibitory activity was removed by exposure to heat or acid pH, or by incubation with chymotrypsin or staphylococcal V8 protease. Contra-IL-1 did not inhibit IL-2- or IL-4-dependent proliferation of murine T cell lines. Despite its ability to inhibit IL-1 activity, contra-IL-1 did not interfere with the binding of recombinant IL-1 beta to a fibroblast cell line. Contra-IL-1 inhibited the proliferation of normal peripheral blood mononuclear cells to both concanavalin A and tetanus toxoid; inhibition could be attenuated by the addition of exogenous IL-1. Messenger RNA extracted from infected macrophages was examined by Northern analysis for the presence of message to IL-1 beta. No message was apparent, suggesting that the presence of contra-IL-1 was not obscuring the concomitant release of IL-1. Infected macrophages stimulated with endotoxin generated readily detectable message for IL-1 beta. Spleen macrophages purified from two patients with AIDS complicated by immune thrombocytopenia spontaneously expressed p24 antigen in vitro and released contra-IL-1 activity into the media. Contra-IL-1 may contribute to the immune dysfunction of AIDS.
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PMID:Release of interleukin 1 inhibitory activity (contra-IL-1) by human monocyte-derived macrophages infected with human immunodeficiency virus in vitro and in vivo. 326 91

Many biologically important peptide sequences contain proline. It confers unique conformational constraints on the peptide chain in that the side-chain is cyclized back onto the backbone amide position. Inside an alpha-helix the possibility of making hydrogen bonds to the preceding turn is lost and a kink will be introduced. The conformational restrictions imposed by proline motifs in a peptide chain appear to imply important structural or biological functions as can be deduced from their often remarkably high degree of conservation as found in many proteins and peptides, especially cytokines, growth factors, G-protein-coupled receptors, V3 loops of the HIV envelope glycoprotein gp 120, and neuro- and vasoactive peptides. Only a limited number of peptidases are known to be able to hydrolyze proline adjacent bonds. Their activity is influenced by the isomeric state (cis-trans) as well as the position of proline in the peptide chain. The three proline specific metallo-peptidases (aminopeptidase P, carboxypeptidase P and prolidase) are activated by Mn2+, whereas the three serine type peptidases cleaving a post proline bond (prolyl oligopeptidase, dipeptidyl peptidase IV, and prolylcarboxypeptidase) share the sequential order of the catalytic Ser-Asp-His triade, which differentiates them from the chymotrypsin (His-Asp-Ser) and subtilisin (Asp-His-Ser) families. An endo or C terminal Pro-Pro bond and an endo pre-Pro peptide bond possess a high degree of resistance to any mammalian proteolytic enzyme.
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PMID:Proline motifs in peptides and their biological processing. 760 38

Inflammatory cells in lymph nodes of eighteen patients suffering from culture-proven tuberculous lymphadenitis were examined by histological and immunohistochemical techniques. Ten patients suffered from symptomatic HIV-infection and eight patients were immunocompetent individuals without HIV-1 serology. Characteristic granulomas with or without caseation were observed in eight immunocompetent and four HIV-1-infected patients with less marked lymphopenia of CD4 positive peripheral blood lymphocytes. No epitheloid cell formation was present in lymph nodes of HIV1-infected patients with more severe depression of CD4 positive peripheral blood lymphocyte count. Foamy macrophages were found instead of these cells. While many cells--predominantly lymphocytes--express CD25 (IL-2 receptor) in cases with typical epitheloid granulomas there is no such CD25 expression in cases without any epitheloid cell formation. This result suggest that T cell function is necessary for epitheloid granuloma formation in human tuberculosis. The phenotype of macrophages underwent progressive changes parallel to decreasing numbers of CD4 positive peripheral blood lymphocytes. Foamy macrophages in Mycobacterium avium-intracellulare infection represented an end-stage phenotype. They were positive for S100 protein and they did not express lysozyme, alpha-1-anti-chymotrypsin, L1 antigen (Mac387) and CD4, whereas positivity for HLA-DR, CD68 and Ki-M8 was preserved. In situ immunohistochemical demonstration of IFN-alpha, IFN-beta, TNF-alpha, IL-1 and IL-6 revealed that foamy cells in M. tuberculosis infection were highly active effector cells. They contained higher concentrations of the examined cytokines than epitheloid cells in the lesions of HIV+ and HIV-patients. Corresponding to these findings the histological proof of acid-fast bacilli was generally not successful in typical HIV-associated tuberculosis. The foamy appearance may result from the lipid-rich cell membranes of destroyed acid-fast bacilli. In contrast acid-fast bacilli-packed foamy macrophages in AIDS patients with M. avium-intracellulare (MAI) infection did not produce any of the examined cytokines.
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PMID:Immunohistochemical analysis of cell composition and in situ cytokine expression in HIV- and non-HIV-associated tuberculous lymphadenitis. 771 49

Although multiple forms of the HIV-1 Tat protein are synthesized during infection from alternatively spliced mRNAs, only 72 amino acid residues encoded in the first Tat exon are necessary for full transactivation activity. We used limited proteolytic digestions of proteins expressed in vitro to study the structures of three Tat proteins from isolate HXB2: 72R Tat (first Tat exon); 86R Tat (first and second Tat exons), Tev or TNV (first Tat exon plus Env and Rev exons). For the 86R and Tev proteins, either trypsin or chymotrypsin cleaved the majority of carboxyl residues from the first exon. Moreover, when released from carboxyl residues, the first exon of 86R and Tev was relatively resistant to subsequent proteolysis. The entire 72R Tat protein was relatively resistant to proteolysis. The protease-resistant first exon in all Tat proteins was abolished by EDTA treatment, suggesting that divalent cations are required for its conformation. Our results suggest that the first exon in the 86R, 72R, and Tev proteins is folded into a similar structure which, as defined by partial proteolysis, acts as a single biochemical domain.
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PMID:Limited proteolytic digestions identify common structural features of HIV-1 Tat proteins expressed during infection from alternatively spliced mRNAs. 845 40

Replication and storage of virus are characteristic features of hyperplastic lymphoid tissues in HIV infection. In opportunistic infections, HIV is synthesized by phagocytic mononuclear and Langhans'-type multinucleated macrophages that coexpress the dendritic cell-associated S-100 and p55 antigens. However, similar cells in hyperplastic tonsils and adenoids from HIV+ individuals were alternatively identified as macrophages or, on the basis of the same S-100 and p55 staining, as dendritic cells. To consider establishing the role of these HIV-rich cells in HIV disease, it is important to reconcile this apparent discrepancy in identity. Hyperplastic tonsils and adenoid specimens were analyzed by HIV RNA in situ hybridization (ISH), light and transmission electron microscopy (TEM), and immunohistochemistry (IHC) (HIV Gag p24 protein, S-100, p55, CD68, HAM56, lysozyme, alpha-1-anti-trypsin, and alpha-1-anti-chymotrypsin). In HIV+ pediatric and adult surgical specimens (n = 11), the giant cells and their mononuclear counterpart were positive for both macrophage and p55 and S-100 IHC markers. In addition, TEM, p24 IHC, and ISH showed HIV expression by cells with typical features of macrophages. Furthermore, these cells were not unique to HIV+ specimens, being seen in 20% of hyperplastic T&A surgical specimens (n = 57) lacking HIV as well as in several types of granulomatous processes, such as sarcoidosis. These cells appear to represent an activated phenotype that can develop independent of HIV, but that may represent a viral host in HIV-infected individuals. Thus, the giant and mononuclear cells that produce striking amounts of HIV in tonsils and adenoids are of macrophage origin, yet, as in opportunistic infections, share dendritic cell-associated antigens, reflecting a common CD34+ bone marrow progenitor.
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PMID:The macrophage origin of the HIV-expressing multinucleated giant cells in hyperplastic tonsils and adenoids. 1036 2

Secretory leucocyte protease inhibitor (SLPI) is a potent inhibitor of granulocyte elastase and cathepsin G, and also an inhibitor of pancreatic enzymes like trypsin, chymotrypsin and pancreatic elastase. SLPI has also been shown to inhibit HIV-1 infections by blocking viral DNA synthesis. Since SLPI is an inhibitor of pancreatic proteases we wished to investigate whether SLPI was also actually produced in the pancreas. M-RNA from human pancreatic tissue showed evidence of SLPI production using the reverse transcriptase polymer chain reaction technique (RT-PCR). Using immunohistochemical methods SLPI was demonstrated in the beta-cells of the islets of Langerhans. The function could be local protease/antiprotease regulation or antiviral/antibacterial defence in the close vicinity of the cell surface, or even inside the beta-cell itself.
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PMID:Production of secretory leucocyte protease inhibitor (SLPI) in human pancreatic beta-cells. 1070 52


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