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

A recombinant vaccinia virus in which the transcription of the human immunodeficiency virus type 1 (BRU isolate) env gene is driven by the 11K late vaccinia promoter yields about 10-fold higher amounts of gp160 env protein upon infection of monkey cells than does a recombinant in which gp160 is expressed using the 7.5K early-late promoter. The gp160 was purified from detergent lysates of infected cells by lentil lectin affinity chromatography followed by immunoaffinity chromatography, and was obtained in yields of 1-2 mg/10(9) cells of material estimated to be about 70% pure. Pairs of rabbits were immunized with purified gp160 using either one of five different adjuvants or an immunostimulating complex. In all cases a substantial humoral immune response was obtained after boosting, including an activity that neutralized the homologous (BRU) isolate of HIV-1. In some cases, this activity also neutralized two distantly related isolates, SF2 and MN.
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PMID:Cross-neutralizing antibodies in rabbits immunized with HIV-1 gp160 purified from simian cells infected with a recombinant vaccinia virus. 174 74

Anti-human immunodeficiency virus type 1 (Anti-HIV-1) antibody response was compared in four groups of mice following inoculation with HIV-1 gp160, with live recombinant vaccinia virus expressing HIV-1 envelope glycoproteins, or with both immunogens in alternate orders for primary or secondary immunizations. Both subunit and recombinant virus immunogens induced similar levels of antibody response following primary immunization. However, after secondary immunization, mice primed with live recombinant virus and then boosted with subunit gp160 immunogen showed significantly higher antibody response than those in the other three groups. Neutralizing antibodies were generated only in this group of mice and were shown to neutralize both the homologous virus (BRU) and a divergent isolate (SF2) of HIV-1. On the other hand, their reactivities to peptide sequences from the principal neutralizing determinant (PND) of gp120 were limited to the BRU isolate, not SF2 or MN, indicating that the cross-neutralizing activities were directed against determinants other than the linear epitope(s) within the PND. These results also indicate that combined immunization by priming with liver recombinant virus and boosting with subunit immunogen may be more effective than immunization by either immunogen alone.
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PMID:Neutralizing antibodies against HIV-1 BRU and SF2 isolates generated in mice immunized with recombinant vaccinia virus expressing HIV-1 (BRU) envelope glycoproteins and boosted with homologous gp160. 176 63

The crystal structure of the aspartyl protease encoded by the gene pol of the human immunodeficiency virus (HIV-1, isolate BRU) has been determined to 2.7 A resolution. The enzyme, expressed as an insoluble denatured polypeptide in inclusion bodies of Escherichia coli has been renatured and crystallized. It differs by several amino acid replacements from the homologous enzymes of other HIV-1 isolates. A superposition of the C alpha-backbone of the BRU protease with that of the SF2 protease gives a roots mean square positional difference of 0.45 A. Thus, neither the denaturation/renaturation process nor the amino acid replacements have a noticeable effect on the three-dimensional structure of the BRU protease or on the detailed conformation of the catalytic site, which is very similar to that of other aspartyl proteases.
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PMID:The three-dimensional structure of the aspartyl protease from the HIV-1 isolate BRU. 179 32

A phase 1 trial of a candidate human immunodeficiency virus type 1 (HIV-1) vaccine was done in 25 healthy seronegative subjects. The antigen, env2-3 (SF2), was a nonglycosylated polypeptide representing the gp120 region of the env gene of the HIV-1(SF2) isolate. It was produced in genetically engineered yeast as a denatured molecule incapable of binding CD4. A synthetic lipophilic muramyl tripeptide (MTP-PE) was used as an adjuvant. Ten subjects received adjuvant alone and 15 received 50- or 250-micrograms doses of env2-3 (SF2) administered intramuscularly in two immunization regimens. In general, adjuvant and vaccine were well tolerated. Antibody responses to both the homologous antigen, env2-3 (SF2), and antigens from other highly divergent HIV isolates were elicited in the majority of vaccine recipients. However, antibody titers were low, without neutralizing activity. In 9 of 11 subjects who received the complete vaccine immunization series, a significant specific T lymphocyte response was observed.
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PMID:Safety and immunogenicity of a genetically engineered human immunodeficiency virus vaccine. 198 6

Severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice) have inducible human immune function and may be useful as a small animal model for acquired immunodeficiency syndrome (AIDS) research. Hu-PBL-SCID mice infected with human immunodeficiency virus-1 (HIV-1) contained virus that was recoverable by culture from the peritoneal cavity, spleen, peripheral blood, and lymph nodes for up to 16 weeks after infection; viral sequences were also detected by in situ hybridization and by amplification with the polymerase chain reaction (PCR). Mice could be infected with multiple strains of HIV-1, including LAV-1/Bru, IIIB, MN, SF2, and SF13. HIV-1 infection affected the concentration of human immunoglobulin and the number of CD4+ T cells in the mice. These results support the use of the hu-PBL-SCID mouse for studies of the pathogenesis and treatment of AIDS.
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PMID:Human immunodeficiency virus infection of human-PBL-SCID mice. 199 Apr 41

The gp120 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) is a dominant target against which the host's humoral immune response is directed. Unfortunately, gp120 proteins from different isolates of HIV are antigenically distinct, complicating the use of the envelope glycoprotein in vaccines designed to prevent acquired immunodeficiency syndrome. Using an enzyme-linked immunosorbent spot assay (ELISA), BALB/c mice immunized and boosted with recombinant purified gp120 were studied at the single cell level for their humoral immune response to HIV-1 envelope proteins. Approximately 90% of responding B cells produced antibodies reactive with the immunizing form of gp120 but not with gp120s from other strains of HIV. A novel sandwich ELISA was then used to analyze the frequency with which individual in vivo activated B cells produced antibodies that crossreacted with heterologous gp120s. Repeated immunizations with a single gp120 or with a mixture of different gp120s resulted in the activation of primarily mono-specific (noncrossreactive) B cells. In contrast, the sequential immunization of mice with recombinant purified envelope proteins from different strains of HIV (IIIB, SF2, and Zr6) induced the selective expansion of B cells producing highly crossreactive antibodies.
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PMID:Sequential immunizations with rgp120s from independent isolates of human immunodeficiency virus type 1 induce the preferential expansion of broadly crossreactive B cells. 200 56

Antisense RNA can inhibit the expression of messenger RNAs (mRNAs) to which they are complementary by a variety of mechanisms and might provide the basis for antiviral therapies of high selectivity. In a previous study of six retrovirally expressed antisense RNAs targeted to HIV-1IIIB, we found that two significantly reduced HIV-1IIIB replication. Here we test the degree to which this inhibitory effect tolerates the natural variation found in the nucleotide sequence of different strains of HIV-1. We show that the longer of the two inhibitory antisense RNAs (600 bases) inhibits replication of HIV strains RF, MN and SF2 to at least as great an extent as it does the homologous strain. In contrast, the shorter (71 bases) does not inhibit replication of the heterologous strains. An examination of the predicted positions of the mismatches in the duplexes formed between the IIIB antisense RNAs and the mRNAs of heterologous strains suggests that one requirement of an inhibitory antisense RNA is that it can form a perfect duplex with its target mRNA of at least some 51-64 base-pairs. Although the observations presented here are not definitive proof of this, they are reminiscent of the structural requirements deduced for the double-stranded RNA-mediated induction of interferon and the activation of interferon-induced 2', 5'-oligo(A) synthetase and protein kinase. We tested the ability of antisense RNA to inhibit HIV replication in Jurkat, CEM, U937 and HeLa-T4 cells. The level of inhibition of HIV-1IIIB replication varied according to the cell line in which it was expressed, but in all cases was significant.
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PMID:Inhibition of heterologous strains of HIV by antisense RNA. 203 96

In human immunodeficiency virus type 1 (HIV-1) infected individuals, the antibody response to the external envelope (gp120) is associated with in vitro neutralization. To further characterize the anti-gp120 response, we examined the IgG reactivity of 75 HIV-1-seroconverted and 200 HIV-1-seropositive individuals to deletion mutants of gp120 in an enzyme immunoassay. We used yeast-derived, non-glycosylated recombinant HIV-1 SF2 gp120 equivalent and-variants deleted in variable regions. We observed two distinctive response patterns: IgG non-responders (SF2-V3-restricted responders) and IgG responders to conserved regions of gp120. This divergence in response pattern occurred soon after gag/env HIV-1 antibody seroconversion and persisted in time within an individual. In addition, the SF2-V3-restricted responders had a higher frequency of HIV-1 core antigen positivity and HIV-1 core antibody negativity than the non-restricted responders. These results suggest that specific and persistent host antibody response patterns to gp120 develop early in HIV-1 infection and that these patterns are associated with differences in HIV-1 expression.
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PMID:Antibody reactivity to deletion mutants of the HIV-1 SF2 envelope. 204 May 87

Variants of the envelope gene of the HIV-SF2 isolate of HIV-1 with deletions of one or more of the hypervariable domains of gp120 were produced in genetically engineered yeast as nonglycosylated denatured polypeptide analogs of gp120. Purified antigens were used to immunize experimental animals to determine whether the removal of hypervariable regions from this type of gp120 immunogen had any effect on (1) the ability of the antigen to elicit virus neutralizing antibodies; and (2) the isolate specificity of the neutralizing antibodies that were elicited. The results of these studies demonstrate that, in addition to the previously identified V3 domain, at least two other hypervariable regions in gp120 are capable of eliciting neutralizing antibodies in experimental animals. However, when all five of the hypervariable regions were deleted, the resulting antigen was no longer capable of eliciting neutralizing antibodies. Finally, the neutralizing antibodies elicited by all of these nonglycosylated antigens were effective against HIV-SF2, the isolate from which the antigens were derived, but were not able to neutralize two divergent isolates, HIV-BRU or HIV-Zr6.
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PMID:Importance of hypervariable regions of HIV-1 gp120 in the generation of virus neutralizing antibodies. 239 Mar 35

Antibodies elicited by HIV-1 strains, and which neutralize such strains in vitro, bind to synthetic peptides of 5-8 amino acids in length. These amino acids, although variable, have a fixed location between two cysteines in the carboxyl terminus of the HIV-1 external envelope. Nine peptides of 9 amino acids corresponding to the gp120 domains of European and American (LAV-1, NY5, CDC4, SF2), Haitian (RF) and African (ELI, MAL, Z3, Z6) HIV-1 strains, were synthesized using LAV-1 and RF neutralization epitopes as models. Serum of chimpanzees infected with LAV-1, HTLV-IIIB or HTLV-IIIRF reacted predominantly with the homologous peptide, although cross-reactivity with heterologous peptides occurred: 8 out of 11 human sera with HTLV-IIIB-neutralizing activity bound the LAV-1/HTLV-IIIB peptide, and 6 out of 7 sera with HTLV-IIIRF-neutralizing activity bound the RF peptide. African sera reacted most frequently with the Z3 peptide (78%) while only 35% (p = 0.0001) of European and 20% (p less than 0.0001) of American sera recognized it. Recognition patterns of children from the USA and Europe were different. Although multiple reactivities were observed, blocking experiments favoured cross-reactivity as the explanation. Based on the antibody profiles of nonapeptide recognition, peptides LAV-1, RF and SF2 were clustered, as were NY5 and CDC4, and so were Z6, MAL and ELI. This antigenic relatedness of HIV-1 strains could not entirely be explained by the physico-chemical characteristics of the nonamers per se. Resemblance was observed with the clustering of HIV-1 strains based on the divergence of the nucleotide sequence of entire HIV-1 envelopes. This implies a role of peripheral envelope residues, in the context of infectious particles or infected cells, in determining the specificity of antibodies reactive to the V3 domain. Therefore, the neutralization domain in this variable region may be considered part of a conformational structure involving several envelope regions which appear distinct from each other in the primary sequence.
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PMID:Antibody recognition of amino acid divergence within an HIV-1 neutralization epitope. 247 66


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