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)

Local secretory immunity in the vagina may confer a degree of protection against heterosexual transmission of human immunodeficiency virus (HIV). Since the vagina has been shown to respond to local immunization, we have undertaken intravaginal immunization of rats with a 20-mer peptide (amino acid residues 102 to 121) of the HIV-1 envelope glycoprotein (gp120). The peptide was administered in combination with an 'absorption enhancer', lysophosphatidyl glycerol (LPG), which has previously been shown to promote the absorption of intravaginally administered peptides, while exerting only mild effects on epithelial membrane integrity. Intravaginal immunization with LPG and the peptide induced serum and vaginal wash IgA and IgG antibody responses which were enhanced in comparison to those after immunization with the peptide alone. Serum antibodies induced by both subcutaneous and intravaginal immunization were able to recognize recombinant HIV-1 gp120. However, the rat antiserum displayed no neutralizing activity against the virus. These results demonstrate that LPG is an effective immunological adjuvant for intravaginally administered peptide antigens. An alternative absorption enhancer, bestatin (BES), was not effective as an immunological adjuvant when administered intravaginally and blocked the adjuvant activity of LPG when BES and LPG were used in combination.
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PMID:Vaginal immunization of rats with a synthetic peptide from human immunodeficiency virus envelope glycoprotein. 164 52

The intracellular transport and fate of nucleic acids is poorly understood. To study this process, we injected fluorescent oligodeoxyribonucleotides (oligos) into the cytoplasm of CV-1 epithelial cells and primary human fibroblasts. Rapid nuclear accumulation was found with the phosphodiester (PD), phosphorothioate (PT), and methylphosphonate (MP) forms of a 28-mer oligo complimentary to the rev mRNA of the human immunodeficiency virus type 1. Migration of the oligos in the cytoplasm was slower than diffusion of a coinjected dextran, but the oligos freely diffused into the nucleus. Nuclear incorporation was temperature but not energy dependent. The intranuclear distribution of the oligos was influenced by the chemistry of internucleoside linkages. The PD oligos and, to a lesser extent, the PT oligos colocalized with small nuclear ribonucleoproteins (snRNPs), whereas the MP oligos colocalized with concentrated regions of genomic DNA. These data have important implications for our understanding of the transport and accumulation of exogenous nucleic acids in mammalian nuclei, and the assay described could potentially be used for testing the efficacy of oligos designed as therapeutic agents.
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PMID:Rapid nuclear accumulation of injected oligodeoxyribonucleotides. 170 81

Delineation of major T helper cell recognition sites of human immunodeficiency virus (HIV-1) proteins represents one important step in the design of an efficient acquired immune deficiency syndrome (AIDS) vaccine. Towards this end, we have explored the immunogenicity of HIV-1BRU proteins in the mouse model. Preliminary experiments revealed that inbred mice primed with whole inactivated HIV-1 developed strong CD4+ T cell proliferative responses to a variety of recombinant viral proteins including reverse transcriptase (RT). To characterize further the mouse T cell responses to this protein, several Ad- or Ed-restricted T hybridoma cells (THC) were established from BALB/c or DBA/2 mice. These THC were tested for their capacity to recognize a series of 15-mer synthetic overlapping peptides spanning three segments of HIV-1 RT that had been preselected on the basis of either alpha-helicity, amphipaticity, and/or for containing rare amino acid sequence patterns. Peptides corresponding to a C-terminal region (residues 528-560) of RT were recognized by several of the THC established from RT-primed mice. Furthermore, a non-alpha-helical peptide from this region (A3, 528-543) was capable of priming mice with different H-2 haplotypes for both peptide A3 and native RT CD4+ T cell recognition. In addition to the recently identified RT determinant 203-219 capable of triggering both mouse and human CD8+ CTL, the present results identify a good candidate for an immunodominant RT epitope capable of eliciting RT-specific T helper cell responses.
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PMID:Identification of a major human immunodeficiency virus-1 reverse transcriptase epitope recognized by mouse CD4+ T lymphocytes. 171 May 63

Polyanionic compounds were used to inhibit infectivity of human immunodeficiency virus in vitro. Suramin, Evans blue, and Trypan blue were shown to inhibit syncytia formation normally observed when HIV-1-infected cells are cocultured with CD4+ cells. The inhibition was more pronounced with Evans blue than with any of the other polyanions studied. The inhibitory effect was significantly weaker in HIV-2 systems. However, the reverse transcriptase activities of both types of viruses were inhibited by Evans blue. Another polyanionic compound, phosphorothioate 28-mer cytidine homopolymer (SdC28) was shown to inhibit syncytium formation induced by HIV-1-and HIV-2-infected cells in an identical manner. Evans blue showed partial blocking of gp120 binding to CD4 in a solid-phase enzyme-linked immunosorbent assay (ELISA). These results suggest that the polyanionic dyes may exert their antiviral effects, at least in part, by interfering with the binding and fusion of HIV with susceptible T cells.
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PMID:Effect of Evans blue and trypan blue on syncytia formation and infectivity of human immunodeficiency virus type I and type II in vitro. 171 43

Complementary 18-mer oligodeoxynucleotides (oligonucleotides) specifically inhibited the formation of human immunodeficiency virus Rev-Rev-response element (RRE) complexes. Inhibition of Rev-RRE binding required blockage of G-7819 to G-7820 in band shift assays. Structural studies revealed both local and distal effects. RRE structure was also disrupted by oligonucleotides targeted to other minor stems, by altering RNA renaturation conditions, or by reducing Rev concentrations--indicating a dynamic RRE structure and involvement of a minor RRE stem in the maturation of initial Rev-RRE complexes. Thus, complementary oligonucleotides alter RRE structure and may prove useful for the design of therapeutic anti-RRE oligonucleotides.
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PMID:Inhibition of human immunodeficiency virus type 1 Rev-Rev-response element complex formation by complementary oligonucleotides. 172 4

The combination of S-dC28 (a phosphorothioate oligodeoxcytidine 28 mer) with AZT, recombinant interferon alpha-A (IFN-alpha A) or dextran sulfate (DS) against replication of human immunodeficiency virus type 1 (HIV-1) were studied in MT4 cells, using both p24 core antigen and reverse transcriptase (RT) assays. Under the standardized conditions, the anti-HIV-1 dose-effect relationships of all test drugs showed sigmoidal curves with the following EC50 values: for the p24 core antigen assay, S-dC28, 0.03 microM; AZT, 0.004 microM; IFN-alpha A, 9.2 U/ml; DS, 0.26 micrograms/ml; for the RT assay, S-dC28, 0.04 microM; AZT, 0.01 microM; IFN-alpha A, 11.6 U/ml; and DS, 0.31 micrograms/ml. A computer software based on the median-effect principle and isobologram techniques were used to quantitatively analyze drug interactions by calculating the combination index (CI) where CI less than 1, = 1, and greater than 1 indicates synergism, additive effect and antagonism, respectively. For p24-ELISA, the interaction of S-dC28 and AZT in combination produced a slight antagonism on HIV-1 replicative inhibition with CI values of 1.29-1.10; for RT assays, at EC50-EC95 levels, the CI values are 1.96-1.11. For p24 core antigen assay, the combination of S-dC28 with IFN-alpha A exhibited a dose-dependent anti-HIV synergism with CI values of 1.15-0.87 at EC75-EC95 levels. The RT assays for the same combination showed a broad synergistic effect with CI values of 0.62-0.60, at EC50-EC95 levels. S-dC28 plus DS showed a nearly additive effect based on both assay methods.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential alteration of the anti-HIV-1 effect of phosphorothioate oligonucleotide S-dC28 by AZT, interferon-alpha, and dextran sulfate. 176 Feb 31

Raw wastewaters were obtained from the cities of Belle Glade, Ocala and Gainesville in the state of Florida and were concentrated using several established methods for the recovery of human enteroviruses. The nucleic acids were then extracted from the wastewater concentrates, suspended in 2 x SSC with and without 2 N NaOH (for the detection of DNA and both DNA and RNA, respectively), and dot blotted onto hybridization membranes. These membranes were then hybridized with three 32P-end-labeled 18-mer oligonucleotides directed against the LTR, gag, and env regions of the human immunodeficiency virus type 1 (HIV-1). Autoradiographic analyses of these blots indicate that sequences homologous to HIV-1 genomic RNA and proviral DNA were found in Belle Glade wastewater but not in wastewater from Ocala and Gainesville. These findings may have implications in the wastewater treatment system as well as for detection of HIV-1 in clinical samples.
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PMID:Detection of nucleic acids homologous to human immunodeficiency virus in wastewater. 178 78

Heterotypic adhesion of T lymphocytes to monocytes, B lymphocytes, or other target cells is mainly mediated by LFA-1 and CD2 molecules. Low-affinity binding of resting T cells can be transiently up-regulated by cross-linking of CD3. We have previously found that binding of specific ligands to CD4 can down-regulate adhesion of resting T cells to B cells. We now show that the enhanced adhesiveness of CD4+ T cells induced by CD3 cross-linking using plastic-bound anti-CD3 antibody can also be inhibited by several CD4 ligands. i.e. anti-CD4 antibodies, the gp160 env protein of human immunodeficiency virus, as well as by putative CD4 ligands, i.e. synthetic peptides analogous to the gp160-binding site to CD4 (positions 418-434 and 449-464) and a 12-mer synthetic peptide (DR-12) analogous to positions 35-46 of HLA class II beta subunit and including the highly conserved Arg-Phe-Asp-Ser (RFDS) sequence. After CD3 cross-linking, maximal binding of T cells to HLA class II-positive and -negative B cells was similar, although binding to HLA class II-negative B cells was more prolonged. T cells that were passively induced to up-regulate adhesion by binding of a CD11a-specific antibody NKIL16, known to enhance LFA-1-dependent adhesiveness, were less sensitive to the inhibitory effect of the DR-12 peptide, whereas the inhibitory effects of gp160 were preserved. The kinetics of adhesion of NKIL16-pretreated T cells was not influenced by HLA class II expression at the B cell surface. Together, these results strongly suggest that CD4-HLA class II interaction may down-regulate low-affinity adhesion of resting T cells and, to some extent, high-affinity adhesion of T cells actively induced by CD3 cross-linking but not passively induced by an anti-CD11a antibody.
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PMID:Regulation of LFA-1-mediated T cell adhesion by CD4. 182 86

Monoclonal antibodies (MAbs) raised against a 15-mer peptide representing the centre of the principal neutralization domain of human immunodeficiency virus type 1 (strain BH10) showed wide variations in neutralizing activity against the homologous strain. The nature of this difference in neutralizing activity was studied by measuring antibody concentration, their affinity for peptide and specificity, by reaction with peptides which differed in the extent of sequence overlap, length and the presence of single amino acid replacements. All MAbs bound to approximately the same region in the principal neutralization domain, within the sequence RIQRGPGRAFV. The peptides with which each antibody was able to react differed by only a few amino acids. The neutralizing activity of each MAb preparation was related to its affinity and concentration; the affinity is related in part to the fine structure of the epitope recognized. MAbs with high affinity for the peptide tended to react only with peptides in which amino acid replacements did not affect the beta-turn potential of the peptide, whereas the reactivity of MABs with low affinity was relatively insensitive to amino acid replacements affecting the beta-turn potential.
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PMID:Neutralizing activity of anti-peptide antibodies against the principal neutralization domain of human immunodeficiency virus type 1. 191 29

Thirty-six monoclonal antibodies from mice and three from rats were raised against a peptide corresponding to the immunodominant domain of the transmembrane gp41 protein of human immunodeficiency virus (HIV) type 1 (LGLWGCSGKLIC; amino acid residues 598 to 609). Of these, three monoclonal antibodies from the mice and one from a rat also reacted with the corresponding peptide derived from the HIV type 2 transmembrane gp41 protein (amino acid residues 593 to 603; NSWGCAFRQVC). Immunochemical studies using a variety of synthetic peptides indicated that the cross-reactivity was due to antibody binding to CSGKLIC of HIV type 1 or CAFRQVC of HIV type 2. Single amino acid substitutions for a cysteine at either the amino or the carboxy end of the peptide interrupted antibody binding, indicating that the site recognized was the Cys-XXXXX-Cys loop. Similar results were obtained when the 11-mer HIV type 2 gp41 peptide (amino acids 593 to 603) was inoculated into mice to raise monoclonal antibodies. In this instance, of 30 monoclonal antibodies developed, 4 reacted with both HIV type 1 and HIV type 2 peptides. The conformation of a seven-residue peptide, CSGKLIC, corresponding to residues 603 to 609 of the gp41 immunodominant epitope of HIV-1 was investigated by proton nuclear magnetic resonance spectroscopy. The immunologically active form of CSGKLIC contains an intramolecular disulfide bond and maintains a preference for a folded conformation, apparently including a type I reverse turn about the residues SGKL. No such preference is observed for the reduced form of the peptide, which contains two thiol groups. The presence of the disulfide bond is thus integral to the formation of the structure of the loop in solution. In agreement with this finding, elimination of the possibility of loop formation by substitution of S for C at the amino or carboxy termini of the 7-mer is accompanied by the failure of antibody binding to this peptide.
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PMID:Mapping the anatomy of the immunodominant domain of the human immunodeficiency virus gp41 transmembrane protein: peptide conformation analysis using monoclonal antibodies and proton nuclear magnetic resonance spectroscopy. 200 40


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