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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell lines secreting IgG1 human monoclonal antibodies (mAb) to the envelope glycoprotein, gp120, of human immunodeficiency virus (HIV) have been produced by transformation of peripheral blood cells from HIV-infected individuals and by fusion of transformed cells to a human-mouse heteromyeloma cell line (SHM-D33). Two human mAbs were site-selected by means of a 23-mer synthetic peptide spanning a portion of the third variable domain of gp120 from the MN strain of HIV. The two heterohybridomas produce three times more IgG than do their parent lymphoblastoid cell lines. The specificities of these mAbs have been mapped to sequences near the tip of the disulfide loop of the gp120 third variable domain, Lys-Arg-Ile-His-Ile and His-Ile-Gly-Pro-Gly-Arg, respectively. The mAbs have dissociation constants of 3.7 x 10(-6) M and 8.3 x 10(-7) M, neutralize HIVMN in vitro at nanogram levels, and bear the characteristics of antibodies associated with protective immunity in vivo.
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PMID:Production of site-selected neutralizing human monoclonal antibodies against the third variable domain of the human immunodeficiency virus type 1 envelope glycoprotein. 201 46

Base-pair sequences in double-stranded DNA can be recognized by homopyrimidine oligonucleotides that bind to the major groove at homopurine.homopyrimidine sequences thereby forming a local triple helix. To make oligodeoxynucleotides resistant to nucleases, we replaced the natural (beta) anomers of the nucleotide units by the synthetic (alpha) anomers. The 11-mer alpha oligodeoxynucleotide 5'-d(TCTCCTCCTTT)-3' binds to the major groove of DNA in an antiparallel orientation with respect to the homopurine strand, whereas a beta oligonucleotide adopts a parallel orientation. When an intercalating agent was attached to the 3' end of the alpha oligodeoxynucleotide, a strong stabilization of the triple helix was observed. A 16-base-pair homopurine.homopyrimidine sequence of human immunodeficiency virus proviral DNA was chosen as a target for a 16-mer homopyrimidine alpha oligodeoxynucleotide. A restriction enzyme that cleaves DNA at the junction of the homopurine.homopyrimidine sequence was inhibited by triple-helix formation. The 16-mer alpha oligodeoxynucleotide substituted by an intercalating agent was approximately 20 times more efficient than the unsubstituted oligomer. Nuclease-resistant alpha oligodeoxynucleotides offer additional possibilities to control gene expression at the DNA level.
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PMID:Triple-helix formation by alpha oligodeoxynucleotides and alpha oligodeoxynucleotide-intercalator conjugates. 206 79

The IgG response to gp41 (envelope glycoprotein of Mr 41,000) of the human immunodeficiency virus (HIV) was studied with eight synthetic peptides derived from three different regions of the protein. We tested sera from 17 HIV-seronegative and 68 HIV-seropositive subjects in an enzyme immunoassay. No HIV antibody-negative serum reacted with any of the peptides. The peptide HIV-env 583-599 has a sequence similarity with immunosuppressive peptides derived from the transmembrane proteins of other retroviruses. Antibodies to this 17-mer (HIV-env 583-599; hereafter also referred to as pHIVIS, putative HIV immunosuppressive sequence) were detected in 27 of the 35 sera from healthy HIV-positive persons but only in 1 of the 33 sera from patients with HIV-related disease. Another 17-mer, displaced four amino acids N-terminally from pHIVIS, reacted with fewer of the sera from healthy seropositive subjects than pHIVIS but with no serum from ill seropositive patients. HIV-env 586-603, which shares two-thirds of its sequence with pHIVIS, reacted with the sera from nearly all subjects, regardless of clinical status. The remaining five peptides did not discriminate between healthy and ill seropositive subjects either but gave lower reactivity rates. HIV-positive sera thus exhibited distinct patterns of reactivity with subsequences of gp41. We have mapped two overlapping epitopes within a narrow part of gp41; antibodies to the most N-terminally located of the two--i.e., the pHIVIS-reactive antibodies--might counteract a possible immunosuppressive effect of gp41.
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PMID:Presence of antibodies to a putatively immunosuppressive part of human immunodeficiency virus (HIV) envelope glycoprotein gp41 is strongly associated with health among HIV-positive subjects. 245 99

A family of oligonucleotides and phosphorothioate oligonucleotide analogues was synthesized with a cholesteryl group tethered at the 3'-terminal internucleoside link. This modification, introduced to enhance interaction of the polyanions with cell membranes, significantly increases the antiviral activity of the oligomers, as judged by inhibition of syncytia formation and expression of viral proteins p17, p24, and reverse transcriptase for human immunodeficiency virus 1 in Molt-3 cells. In the most favorable case, with a 20-mer cholesteryl-phosphorothioate derivative, complete inhibition by all assays was obtained with an oligomer concentration of 0.2 microM. Even decamers were active, and some antiviral activity was observed for a heptanucleotide cholesteryl-phosphorothioate derivative, which binds very poorly to complementary oligonucleotides. These facts, and the finding that the activity of the phosphorothioate decamers does not correlate with a specific sequence, suggests that a mechanism other than "antisense inhibition" may be operative in these systems.
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PMID:Cholesteryl-conjugated oligonucleotides: synthesis, properties, and activity as inhibitors of replication of human immunodeficiency virus in cell culture. 277 42

Nuclease-resistant phosphorothioate analogs of certain oligodeoxynucleotides have been tested in vitro as antiviral agents against human immunodeficiency virus (HIV) in human T cells. Phosphorothioate analogs complementary to HIV sequences, as well as noncomplementary analogs including homooligomers, exhibited potent antiviral activity. The antiviral activity was related to the base composition of the analogs, and longer phosphorothioates were more effective than shorter ones. A 28-mer phosphorothioate oligodeoxycytidine (S-dC28) at a concentration of 1 microM exhibited potent antiviral activity and inhibited de novo viral DNA synthesis as shown by Southern blot analysis. However, S-dC28 failed to inhibit gag expression in chronically infected T cells assessed by immunofluorescent assay at concentrations up to 25 microM. An N3-methylthymidine-containing phosphorothioate analog, which does not hybridize efficiently in vitro to complementary normal DNA, showed no antiviral activity. A 14-mer phosphorothioate oligodeoxycytidine (S-dC14) synergistically enhanced the antiviral activity of 2',3'-dideoxyadenosine, an anti-HIV nucleoside. Therefore, phosphorothioate analogs of oligodeoxynucleotides could represent a unique class of experimental therapeutic agents against the acquired immunodeficiency syndrome and related diseases. However, their mechanism of action is likely to be complex.
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PMID:Phosphorothioate analogs of oligodeoxynucleotides: inhibitors of replication and cytopathic effects of human immunodeficiency virus. 349 13

Using a mixture of synthetic 17-mer oligonucleotides encoding the 64 possible sequences for a peptide of adenosine deaminase as probe, we have isolated a clone for adenosine deaminase mRNA sequences from a collection of T-cell cDNA recombinants. This cDNA clone, phADA-1, contains an insert of 0.8 kilobase. In addition to the peptide chosen for synthesis of the oligonucleotide probe, the complete DNA sequence predicts 16 other experimentally determined peptides. Mapping of total cellular human DNAs with several restriction enzymes revealed relatively simple patterns of hybridization with phADA-1 as probe, including a polymorphism for PvuII cleavage. In agreement with previous studies, the adenosine deaminase gene was localized by blot hybridization to chromosome 20 in a hybrid cell mapping panel. Using the cDNA as probe, an 18-kilobase EcoRI fragment of human cellular DNA was also cloned in bacteriophage Charon 4A. These adenosine deaminase clones will prove valuable in the full characterization of the cellular gene, molecular analysis of inherited enzyme deficiency associated with immunodeficiency, and regional mapping of human chromosome 20.
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PMID:Molecular cloning of human adenosine deaminase gene sequences. 668 8

Reverse transcriptases from both human immunodeficiency viruses type 1 and 2 are obligatory dimers. A tryptophan-rich repeat motif that is highly conserved between these proteins, as well as in the reverse transcriptase from simian immunodeficiency virus, has been postulated to be involved in hydrophobic subunit interactions. A synthetic 19-mer peptide covering part of this tryptophan repeat motif was recently shown to inhibit human immunodeficiency viruses type 1 reverse transcriptase subunit dimerization (Divita, G., Restle, T., Goody, R. S., Chermann, J.-C., and Baillon, J. G. (1994) J. Biol. Chem. 269, 13080-13083). In the present study, we show that the same peptide can also inhibit human immunodeficiency virus type 2 reverse transcriptase subunit dimerization, suggesting that the same inhibitors might be used as agents against both viruses as well as against variants of human immunodeficiency virus type 1 that differ from the variant against which they were developed. Under appropriate experimental conditions, e.g. at acidic pH, this peptide is also able to induce the dissociation of the enzyme from human immunodeficiency virus type 1.
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PMID:Interface peptides as structure-based human immunodeficiency virus reverse transcriptase inhibitors. 749 82

The mechanism of human immunodeficiency virus reverse transcriptase-catalyzed strand transfer synthesis (i.e. switching of the primer to a new template) from internal regions of natural sequence RNA was investigated. The system consisted of a 142-nucleotide RNA template (donor) primed with a specific 20-nucleotide DNA oligonucleotide used to initiate synthesis. DNA oligonucleotides with homology to internal regions of the donor were used as acceptor templates. In reactions performed in the absence of acceptor template, a prominent DNA synthesis product 75 nucleotides in length resulting from pausing DNA synthesis within the homology zone was observed. Prominent donor RNA degradation products of 47 or 54 nucleotides were also observed, in reactions with 80 or 150 mM KCl, respectively. The lengths indicated a potential 13- or 20-nucleotide long, respectively, complementary region between the DNA and RNAs. The 54-, but not the 47-, nucleotide RNA was susceptible to Escherichia coli RNase H, indicating that the DNA was annealed only to the 54-mer. When acceptor was added, a portion of the 75-nucleotide DNA was chased into transfer product at both salt concentrations, and a portion of the 54-mer RNA became resistant to E. coli RNase H. Evidently, this donor RNA was annealed to the 75-nucleotide long DNA but could be actively displaced by the acceptor. Overall, these observations support two mechanisms for transfer. In one, the pause site-specific DNA dissociates from the donor template before transferring. In the other, the acceptor actively displaces the DNA from the donor.
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PMID:The mechanism of human immunodeficiency virus reverse transcriptase-catalyzed strand transfer from internal regions of heteropolymeric RNA templates. 750 52

Antibodies have been raised against a synthetic peptide (IRDKIQKENALFRNL) containing a neutralizing epitope within the second variable region of the human immunodeficiency virus type 1 (HIV-1) SF2 strain external envelope glycoprotein (gp120) and also against equivalent peptides of the HIV-1 LAI, RF and MN isolates. The resulting antisera cross-react with heterologous peptides but binding to heterologous recombinant gp120 is more restricted. Antisera to HIV-1 SF2, RF and MN are able to neutralize homologous virus. Some cross-neutralization is also observed, but a consensus peptide failed to induce neutralizing antibodies to any of the isolates studied. Antibodies to the V2 and V3 epitopes give a higher neutralization index when acting together than when the individual sera are used alone. Antibodies induced in natural infection bind to two sets of hexamers within the region encompassed by the 15-mer peptide, and the response to these can differ between infected individuals and within the same host over time.
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PMID:Antisera raised against the second variable region of the external envelope glycoprotein of human immunodeficiency virus type 1 cross-neutralize and show an increased neutralization index when they act together with antisera to the V3 neutralization epitope. 750

Based on presently available information on the structure of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase, peptides have been synthesized which correspond to the sequence of a particular region of the protein involved in formation of the active heterodimeric form of the enzyme. Several peptides that are 15-19 amino acids long and that are derived from the so-called connection domain of the reverse transcriptase are able to inhibit dimerization of the enzyme and thus inhibit development of its enzymatic activities. In particular, a tryptophan-rich 19-mer corresponding to residues 389-407 was relatively efficient, showing an apparent dissociation constant in the micromolar range for one or both of the subunits. The sequence of this region is identical for both subunits, since one (molecular mass of 51 kDa) is the proteolytic product of the other (molecular mass of 66 kDa). Dissociation of the preformed heterodimer could not be induced by the peptides, but increasing concentrations reduced the rate of dimerization in a concentration-dependent manner until it became immeasurable at high concentrations. The results suggest that inhibition of dimerization of reverse transcriptase is an attractive approach to chemotherapeutic intervention in HIV infection and that further development of peptide-based inhibition strategies is worth pursuing.
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PMID:Inhibition of human immunodeficiency virus type 1 reverse transcriptase dimerization using synthetic peptides derived from the connection domain. 751 98


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