Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0001175 (AIDS)
120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two antibodies, affinity-purified from human immunodeficiency virus-positive human plasma with synthetic peptides in the region gp41(566-596), were found to recognize oligomeric gp41 more strongly than the monomeric form in an immunoblot assay. In contrast, a murine anti-gp160 monoclonal antibody, which maps within this sequence to gp41(581-596), recognized only monomeric gp41 after disruption of the oligomer with sodium dodecyl sulfate. This monoclonal anti-gp160 antibody did not recognize chemically crosslinked oligomeric gp41 that had been treated with similar conditions used to disrupt the gp41 oligomer. These results indicate that this epitope is inaccessible to binding by this antibody when gp41 is oligomeric. Cyanogen bromide cleavage of gp41 resulted in a 17-kD fragment Thr-541-Met-631. A significant proportion of this fragment was oligomeric when derived from chemically crosslinked gp41. The region Ala-566-Gln-596, within the cyanogen bromide fragment, contains the oligomerization-sensitive epitopes as well as two lysine residues available for crosslinkage. This region is relatively conserved and has the propensity to form an amphipathic alpha-helix.
AIDS Res Hum Retroviruses 1992 Dec
PMID:Antibody epitopes sensitive to the state of human immunodeficiency virus type 1 gp41 oligomerization map to a putative alpha-helical region. 128 26

Adolescent childbearing increased 16% over 1986-90 in the Southern region of the US from 38.4 to 44.6 births/1000 girls aged 15-17; adolescent birth rates declined only in Oklahoma at the rate of 1%. Southern states spent more than $5.7 billion in Aid to Families with Dependent Children, Medicaid, and food stamps in 1991 to support families started by adolescent mothers, but federal and state spending combined for the primary prevention of adolescent pregnancy totalled only $110 million in the same states. Public expenditures related to adolescent childbearing in Alabama in fiscal year 1991 totalled more than $117 million, yet less than $1.5 million is spent on preventing teen pregnancy. The author stresses the need for stronger state commitment, leadership, and funds for programs to prevent pregnancy. Thus far, Alabama has definitely not done enough to address the HIV and AIDS pandemic.
Ala Med 1992 Dec
PMID:Adolescent pregnancy: a regional tragedy. 129 32

Functional studies assessed the cytolytic activity of the amino terminal peptide (FP-I; 23 residues 519-541) of the glycoprotein 41,000 (gp41) of the Human Immunodeficiency Virus Type-1 (HIV-1). Synthetically prepared FP-I efficiently hemolyzed human red blood cells at 37 degrees C, with 40% lysis at 32 microM. Kinetic studies indicated that FP-I induced maximal hemolysis in 30 min, probably through tight binding of the peptide with the red cell membrane. The Phe-Leu-Gly-Phe-Leu-Gly (residues 526-531) motif in FP-I apparently plays a critical role in lysis of red cells, since no hemolytic activity was observed for an amino-acid-substituted FP-I in which the unique Phe-Leu-Gly-Phe-Leu-Gly was converted to Ala-Leu-Gly-Ala-Leu-Gly. As neither smaller constituent peptides (e.g., residues 519-524 and residues 526-536) nor a N-terminal flanking peptide (e.g., residues 512-523) induced red cell hemolysis, the entire 23-residue (519-541) sequence of FP-I may be required for hemolytic activity. FP-I was also cytolytic with CD4(+)-bearing Hut-78 cells, with 40% lysis at approx. 150 microM. These results are consistent with an earlier hypothesis that the N-terminal peptide of gp41 may partially contribute to the in vivo cytopathic actions of HIV-1 infection (Gallaher, W.R. (1987) Cell 50, 327-328).
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PMID:The amino-terminal peptide of HIV-1 glycoprotein 41 lyses human erythrocytes and CD4+ lymphocytes. 135 63

Structural studies assessed interactions between the amino-terminal peptide (FP-I; 23 residues 519-541) of the glycoprotein 41,000 (gp41) of Human Immunodeficiency Virus Type-1 (HIV-1) and human erythrocyte membranes and simulated membrane environments. Peptide binding was examined at sub-hemolytic (approx. less than 5 microM) and hemolytic (greater than or equal to 5 microM) doses (Mobley et al. (1992) Biochem. Biophys. Acta 1139, 251-256), using circular dichroism (CD) and Fourier-transform infrared (FTIR) measurements with FP-I, and electron spin resonance (ESR) studies employing FP-I spin-labeled at either the amino-terminal alanine (FP-II; residue 519) or methionine (FP-III; position 537). In the sub-lytic regime, FP-I binds to both erythrocyte lipids and dispersions of SDS with high alpha-helicity. Further, ESR spectra of FP-II labeled erythrocyte ghosts indicated peptide binding to both lipid and protein. In ghost lipids, FP-II was monomeric and exhibited low polarity and rapid, anisotropic motion about its long molecular axis (i.e., alpha-helical axis), with restricted motion away from this axis. The spin-label at the amino-terminal residue (Ala-519) is insensitive to the aqueous broadening agent chromium oxalate and buried within the hydrophobic core of the membrane; the angle that the alpha-helix (residues 519-536) makes to the normal of the bilayer plane is either 0 degree or 40 degrees. Contrarily, ESR spectra of ghost lipids labeled with sub-lytic doses of FP-III indicated high mobility and polarity for the reporter group (Met-537) at the aqueous-membrane interface, as well as extreme sensitivity to chromium oxalate. At lytic FP-I doses, CD and FTIR showed both alpha-helix and beta-structure for peptide in ghost lipids or detergent, while ESR spectra of high-loaded FP-II in ghost membranes indicated peptide aggregates. Membrane aggregates of FP-I may be involved in hemolysis, and models are suggested for N-terminal gp41 peptide participation in HIV-induced fusion and cytolysis.
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PMID:The amino-terminal peptide of HIV-1 glycoprotein 41 interacts with human erythrocyte membranes: peptide conformation, orientation and aggregation. 135 64

In a previous experiment a group of 15 specified pathogen free (SPF) cats were experimentally infected with a Swiss isolate of feline immunodeficiency virus (FIV). A group of 15 SPF cats served as FIV negative controls. Nine cats of each group were vaccinated with a recombinant feline leukemia virus (FeLV) vaccine, six cats in each group with a placebo vaccine. All vaccinated cats developed high antibody titers to FeLV and were protected against subsequent FeLV challenge infection. In both control groups five of six cats became persistently infected with FeLV. Unexpectedly, the primary immune response to the vaccine antigen was significantly higher in the FIV positive group than in the FIV negative. The secondary response was stronger in the FIV negative cats. The goal of the present investigation was to further study the immune response in these 30 cats. They were immunized twice with the synthetic peptide L-tyrosine-L-glutamic acid-poly(DL-alanine)-poly(L-lysine) (TGAL) 21 days apart. Blood samples were collected on four occasions during the immunization process. They were tested for antibodies to TGAL, complete blood cell counts and CD4+, CD8+ and pan-T-lymphocyte counts. The following observations were made: (1) in contrast to the FeLV vaccine experiment, the primary immune response to TGAL was not significantly stronger in the FIV positive cats when tested by enzyme-linked immunosorbent assay (2). The absolute size of the CD4+ lymphocyte population was distinctly smaller in the FIV positive than in the FIV negative cats. The lowest CD4+ values were found in the dually FIV/FeLV infected cats. (3) A population of CD8+ lymphocytes was identified that was characterized by a distinctly weaker fluorescence. The size of this population increased in FIV positive and decreased in FIV negative cats during the TGAL immunization experiment. (4) The CD4+:CD8+ ratio increased in FIV negative cats during TGAL immunization from 1.9 to 2.3. In contrast, in FIV positive animals the CD4+:CD8+ ratio decreased significantly from 1.9 to 1.3 during the same period. From these and earlier data it was concluded that in short-term FIV infection the immune response to T-cell dependent antigens may be increased over that of the controls. Immune suppression develops gradually with duration of the infection. The significant drop of the CD4+:CD8+ ratio over a 5 week immunization period suggests that antigenic stimulation may accelerate the development of immune suppression in FIV positive cats. If this is a general feature, FIV infection may provide a particularly interesting model for studying the pathogenesis of AIDS.
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PMID:Immunization-induced decrease of the CD4+:CD8+ ratio in cats experimentally infected with feline immunodeficiency virus. 136 9

Two immunologically distinct glycoproteins, fractions C4 and C6, with a molecular weight of 28,000 and 28,500, respectively, estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were isolated from seeds of Luffa cyclindrica using acetone precipitation, gel filtration on Sephadex G-75, and ion exchange chromatography on CM-Sepharose CL-6B. Fractions C4 and C6 correspond to luffin-a and luffin-b, respectively, according to the ion exchange chromatographic behavior and amino acid compositions. Fraction C6 and luffin-b were characterized by a lower content of threonine and a higher content of proline than fraction C4 and luffin-a. The 2 luffins, the protein from Luffa acutangula (luffaculin) and trichosanthin exhibited an overall similarity in amino acid composition. The proteins differed in the content of aspartic acid, threonine, proline, and alanine but were otherwise similar in amino acid composition. The ribosome inactivating proteins from Luffa cylindrica seeds also possessed abortifacient activity: they were capable of inducing mid term abortion in mice, inhibiting protein synthesis in a cell-free system, and suppressing thymidine uptake by human choriocarcinoma cells. The abortifacient activity of these proteins is possibly the result of their inhibitory effects on the biosynthetic activity of implanting embryos and endometrial cells. Trichosanthin inhibits the replication of human immunodeficiency virus (HIV) in acutely and chronically infected cells of lymphocyte and mononuclear phagocyte lineage with a potential in AIDS therapy. However, it is still unknown whether the proteins from Luffa cylindrica seeds also possess anti-HIV activity.
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PMID:Two proteins with ribosome-inactivating, cytotoxic and abortifacient activities from seeds of Luffa cylindrica roem (Cucurbitaceae). 150 59

In order to determine whether the cysteine requirement of human T lineage cells is met primarily by extracellular cysteine or by cystine, amino-acid-transport activities were measured in resting and mitogenically stimulated human peripheral blood lymphocytes (PBL) and several human T cell clones and T cell tumors. The transport activity of the small neutral amino acids cysteine and alanine (ASC system) and the transport of the cationic amino acid arginine (y+ system) were found to be markedly increased after stimulation of PBL by the T cell mitogen phytohemagglutinin from Phaseolus vulgaris. The anionic transport activity for cystine and glutamate (Xc- system), in contrast, was extremely weak in both resting and activated human PBL and also in all human T cell lines under test. The weak system Xc- activity of human T lineage cells was further confirmed by an independent line of experiments showing that an increase of the extracellular concentration of glutamate, i.e. a competitive inhibitor of cystine transport, causes a decrease in the intracellular cystine levels in cells of the promonocytic line U937, but not in T lineage cells (Molt-4). A third set of experiments showed that the rate of DNA synthesis in mitogenically stimulated human PBL is strongly influenced by variations of the extracellular cysteine level, even in cultures with relatively high and approximately physiological concentrations of cystine. Cysteine cannot be replaced in this case by the addition of corresponding amounts of cystine or methionine. This demonstrates an important functional consequence of the weak cystine transport activity of human lymphocytes. The results may be relevant for the pathogenetic mechanism of the acquired immunodeficiency syndrome, since the mean plasma cysteine concentration of human-immunodeficiency-virus-1-seropositive persons was found to be strongly decreased in comparison with that of healthy blood donors, and since the cysteine level even of healthy persons is extremely low in comparison with all other protein-forming amino acids.
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PMID:Low membrane transport activity for cystine in resting and mitogenically stimulated human lymphocyte preparations and human T cell clones. 168 Jun 78

CD4, a cell surface glycoprotein expressed primarily by T lymphocytes and monocytes, interacts with HLA class II antigens to regulate the immune response. In AIDS, CD4 is the receptor for the human immunodeficiency virus, which binds to CD4 through envelope glycoprotein gp120. Delineation of the ligand-binding sites of CD4 is necessary for the development of immunomodulators and antiviral agents. Although the gp120 binding site has been characterized in detail, much less is known about the class II binding site, and it is as yet uncertain whether they partially or fully overlap. To investigate CD4 binding sites, a cellular adhesion assay between COS cells transiently transfected with CD4 and B lymphocytes expressing HLA class II antigens has been developed that is strictly dependent on the CD4--class II interaction, quantitative, and highly reproducible. Mutants of CD4 expressing amino acids with distinct physicochemical properties at positions Arg-54, Ala-55, Asp-56, and Ser-57 in V1, the first extracellular immunoglobulin-like domain, have been generated and studied qualitatively and quantitatively for interaction with HLA class II antigens, for membrane expression, for the integrity of CD4 epitopes recognized by a panel of monoclonal antibodies, and for gp120 binding. The results obtained show that the mutations in this tetrapeptide, which forms the core of a synthetic peptide previously shown to have immunosuppressive properties, affect the two binding functions of CD4 similarly, lending support to the hypothesis that the human immunodeficiency virus mimicks HLA class II binding to CD4.
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PMID:Mutations in the D strand of the human CD4 V1 domain affect CD4 interactions with the human immunodeficiency virus envelope glycoprotein gp120 and HLA class II antigens similarly. 171 92

The N-terminal region of the human immunodeficiency virus type 1 (HIV-1) gp41 appears to be involved in virus-cell membrane fusion. To study the influence of fusion domain structure on gp41 interaction with artificial lipid membranes, two families of peptides were synthesized. The peptides of the first family starting from the C-terminal Gly-532 of gp160 (BRU isolate) were assembled in a stepwise manner to N-terminus of gp41(Ala-517). These hydrophobic peptides, containing 10-16 amino acid residues (a.a.), were able to form channel-like current fluctuation through planar lipid membranes, and the longest 15-16 a.a. peptides lysed the liposomes. Peptides of the second family beginning from the C-terminal Arg-538 and continuing to Val-510 contained several hydrophilic amino acid residues. These 15-22 a.a. peptides also increased the conductance of planar lipid bilayers and lysed liposomes. The degree of liposome lysis depended upon peptide length and concentration. The attachment of gp120 C-terminal amino acid or peptides to N-terminus of 517-538 peptide resulted in complete loss of activity. The effects of the second family of peptides on membranes were reduced to a great extent at acidic pH. The conjugation of 22 a.a. Lys peptide with bovine serum albumin decreased its lytic activity. The circular dichroism study of these peptides revealed alpha-helix configuration in hydrophobic and aqueous media only for deca- and longer peptides. The electron microscopy of 22 a.a. peptide performed in the aqueous medium showed large spherical aggregates about 0.5-0.7 micron in diameter consisting of long filaments approximately 5 nm in diameter. Other tested peptides could generate only short strings. Thus, the effects of fusion peptides on lipid membranes depends on their sequence and length, secondary and tertiary structures, and freedom of their N-terminus.
AIDS Res Hum Retroviruses 1992 Jan
PMID:Investigation of human immunodeficiency virus fusion peptides. Analysis of interrelations between their structure and function. 173 43

The V3 loop (residues 303-338) of the human immunodeficiency virus type 1 (HIV-1) gp120 envelope protein represents a principal neutralizing determinant for the virus. An HIV-1 proviral clone containing a mutation in the V3 loop was constructed in which the proline residue at position 313 was changed to an alanine (P313-A). This mutation alters the conserved GPGR sequence that is found in the V3 loop sequences of different HIV-1 isolates. The P313-A clone produced virus particles, which were infectious for a number of T-cell lines including MOLT-4, CEM, and SupT1, but demonstrated a relatively low infectivity on the AA5 B-cell line when compared with wild-type viruses, HTLV-IIIB, HXB2/10 (a chimeric molecular clone), and another mutant virus (Q290-T). V3 loop-specific neutralizing polyclonal sera and the 9284 monoclonal antibody, which recognizes the amino side of the V3 loop sequence, effectively blocked infectivity and syncytia formation of all viruses tested. In contrast, the 0.5 beta monoclonal antibody, which is biologically more potent than 9284 and recognizes a different V3 loop determinant, failed to neutralize the P313-A virus. These results suggest that the proline residue in the relatively conserved GPGR "turn" region of the V3 loop is crucial for recognition by the 0.5 beta antibody. The observed variation in sensitivity of the B-cell line to the P313-A virus may reflect the presence of cell-specific factors which could be important in establishing an HIV-1 infection.
AIDS Res Hum Retroviruses 1991 Jul
PMID:Alteration of HIV-1 infectivity and neutralization by a single amino acid replacement in the V3 loop domain. 176 61


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