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

The human immunodeficiency virus type 1 (HIV-1) Rev protein mediates the accumulation of unspliced and singly spliced viral transcripts within the cytoplasm of infected cells, late in the infection cycle, leading to the expression of the viral structural proteins, Gag, Pol, and Env. Rev binds to a complex RNA structure, the Rev-responsive element (RRE), present in all Rev-responsive viral transcripts, relieving their nuclear sequestration. The precise mechanism by which RRE-containing transcripts are retained within the nucleus in the absence of Rev protein is not well understood. We previously demonstrated that the RRE alone plays a crucial role in the nuclear retention of RRE-containing env transcripts in stably transfected Drosophila cells. Here we extend our previous observations and demonstrate that the RRE is a principal determinant of nuclear retention for envelope transcripts in primate cells and, in particular, human CD4+ T cells.
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PMID:The rev-responsive element negatively regulates human immunodeficiency virus type 1 env mRNA expression in primate cells. 870 94

Whole inactivated virus (WIV) vaccines derived from the FLA cell line protect cats against challenge with feline immunodeficiency virus (FIV). To discover whether the protective effects of WIV could be reproduced by the isolated Env component, either WIV or immunoaffinity-purified FIV gp120 from the FL4 cell line was administered to cats. Although both vaccines induced high levels of virus neutralizing antibodies, purified Env was much less effective than WIV in protecting cats against viraemia. However, reduced virus load in PBMCs was evident in all Env-immunized cats compared to controls. Analyses of antibody responses to bacterial expression products of FIV Env, which were high in Env-immunized cats but low in animals receiving the WIV vaccine, suggested that the partially denatured, monomeric Env induces a less effective antiviral immune response than WIV. Hence, the superior immunogenicity of WIV may be due to the presentation of the native oligomeric structure of Env on virions.
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PMID:Suppression of virus burden by immunization with feline immunodeficiency virus Env protein. 873 52

A macaque monkey infected with NM-3, a human immunodeficiency virus type 1 (HIV-1)-simian immunodeficiency virus strain mac (SIVmac) chimeric virus with env, rev, tat and vpu derived from HIV-1 and LTR, gag, pol, vif and vpx derived from SIVmac, became a long-term carrier (more than 2.8 years). This monkey produced neutralizing antibodies to the original NM-3 as well as to the parental HIV-1. The virus recovered at 116 weeks replicated more rapidly and productively in macaque peripheral blood mononuclear cells than the original virus. The recovered virus was not neutralized either by antibodies raised early in the monkey or by a neutralizing monoclonal antibody that recognizes the V3 loop of HIV-1 Env, whereas both the early antibodies and the monoclonal antibody neutralized the original NM-3. Analysis of the virus genomic population revealed a few common mutations in the V3 region that caused amino acid changes. These data are consistent with the hypothesis that the virus escaped from the early antibodies and that the observed mutations contributed to this, as with HIV-1-infected humans. The observed mutations could equally well be the result of adaptation to simian cells. These results suggest that the HIV-1-SIVmac chimeric virus will be useful for investigating genetic variation of HIV-1 env and alteration of biological properties in vivo in relation to the host immune response.
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PMID:Genomic and biological alteration of a human immunodeficiency virus type 1 (HIV-1)-simian immunodeficiency virus strain mac chimera, with HIV-1 Env, recovered from a long-term carrier monkey. 876 Apr 11

Work in this laboratory previously demonstrated that the tropism of different human immunodeficiency type 1 isolates for infection of human CD4+ continuous cell lines (e.g., T-cell lines and HeLa-CD4 transformants) versus primary macrophages is associated with parallel intrinsic fusogenic specificities of the corresponding envelope glycoproteins (Envs). For T-cell line-tropic isolates, it is well established that the target cell must also contain a human-specific fusion cofactor(s) whose identity is unknown. In this study, we tested the hypothesis that the Env fusion specificities underlying T-cell line versus macrophage tropism are determined by distinct cell type-specific fusion cofactors. We applied a recombinant vaccinia virus-based reporter gene assay for Env-CD4-mediated cell fusion; the LAV and Ba-L Envs served as prototypes for T-cell line-tropic and macrophage-tropic isolates, respectively. We examined CD4+ promyeloctic and monocytic cell lines that are infectible by T-cell line-tropic isolates and become susceptible to macrophage-tropic strains only after treatment with differentiating agents. We observed parallel changes in fusion specificity: untreated cells supported fusion by the LAV but not the Ba-L Env, whereas cells treated with differentiating agents acquired fusion competence for Ba-L. These results suggest that in untreated cells, the block to infection by macrophage-tropic isolates is at the level of membrane fusion; furthermore, the differential regulation of fusion permissiveness for the two classes of Envs is consistent with the existence of distinct fusion cofactors. To test this notion directly, we conducted experiments with transient cell hybrids formed between CD4-expressing nonhuman cells (murine NIH 3T3) and different human cell types. Hybrids formed with HeLa cells supported fusion by the LAV Env but not by the Ba-L Env, whereas hybrids formed with primary macrophages showed the opposite specificity; hybrids formed between HeLa cells and macrophages supported fusion by both Envs. These results suggest the existence of cell type-specific fusion cofactors selective for each type of Env, rather than fusion inhibitors for discordant Env-cell combinations. Finally, analyses based on recombinant protein expression and antibody blocking did not support the proposals by others that the CD44 or CD26 antigens are involved directly in the entry of macrophage-tropic isolates.
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PMID:Cell type-specific fusion cofactors determine human immunodeficiency virus type 1 tropism for T-cell lines versus primary macrophages. 876 60

Multibranched peptides (SPCs) derived either from the fusion protein (gp41) sequence or from the cleavage sequence of the human immunodeficiency virus type 1 envelope were chemically synthesized and tested for their ability to inhibit both syncytium formation and HIV production in CD4+ cells. The gp41-derived SPCs had no effect. In contrast, an SPC encompassing the envelope cleavage sites strongly inhibited both HIV Env-induced syncytium formation and viral production.
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PMID:Anti-HIV activity of multibranched peptide constructs derived either from the cleavage sequence or from the transmembrane domain (gp41) of the human immunodeficiency virus type 1 envelope. 880 80

Expression of human immunodeficiency virus (HIV) Gag precursor protein (Pr55) by recombinant baculoviruses in insect cells results in the assembly and budding of Pr55 as virus-like particles, or Gag pseudovirions. The ultrastructural morphology, size, and sucrose sedimentation rate of Gag pseudovirions are indistinguishable from immature lentivirus particles produced by HIV-infected human cells. Recombinant baculoviruses were engineered to express individually Pr55 and HIV Env glycoprotein precursor (gp160). These recombinant baculoviruses were used to co-infect insect cells to produce chimeric HIV Gag pseudovirions containing gp160 in experiments to develop methodologies for producing complex noninfectious particulate vaccines for HIV. Coexpression of HIV Pr55 and gp160 resulted in the apparent incorporation of gp160 into Gag pseudovirions as determined by immunoblotting with envelope-specific monoclonal antibodies. Furthermore, results from indirect immunogold electron microscopy using monoclonal antibodies to HIV gp120, a component of the Env glycoprotein precursor, suggested that HIV gp160 was specifically incorporated during the budding process into the outer surface of chimeric Gag pseudovirions. Parallel labeling experiments to localize gp120 and Pr55 epitopes on HIV-infected H9 lymphocytes provided results similar to those obtained with chimeric Gag pseudovirions producing recombinant baculovirus-infected insect cells. Parameters influencing immunoelectron microscopy results in cell-surface and postembedding labeling experiments are discussed.
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PMID:Immunologic and Ultrastructural Characterization of HIV Pseudovirions Containing Gag and Env Precursor Proteins Engineered in Insect Cells 881 71

We investigated the performance of a double-antigen sandwich recombinant enzyme immunoassay (EIA; Abbott Laboratories, North Chicago, Ill.) and compared it with that of a synthetic-peptide-based EIA (Biochem Immunosystems, Montreal, Quebec, Canada) for the detection of human immunodeficiency type 1 (HIV-1) and HIV-2 antibodies in 2,321 clinical serum samples. The results of both EIA methods and Western blot (immunoblot) were in agreement for 1,046 HIV-1 and 10 HIV-2 specimens from a panel of known positives. From a prospective panel of 1,085 specimens, 38 proved to be positive by both EIAs and Western blot, 3 were positive by the recombinant EIA only, and 9 were positive by the peptide EIA only, for calculated specificities of 99.71 and 99.04%, respectively. Of 180 specimens from a seroconversion panel collected from 77 patients, the results for 170 were in agreement by all antibody testing methods and 10 were found to be repeat reactive for HIV antibodies by the recombinant EIA only. All 10 were initial specimens of seroconverting patients; 7 were also reactive for HIV p24 antigen. An examination of four of these sera by radioimmunoprecipitation assay showed gp120 and gp160 bands in each. Analysis of the anti-Env antibody class in three of these samples showed that one consisted of immunoglobulin M (IgM) only and two contained both IgG and IgM antibodies. Although both EIA procedures were sensitive and specific in the detection of antibodies to HIV-1 and HIV-2 and both were capable of detecting early antibodies, the recombinant assay was more sensitive for antibody detection during early seroconversion.
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PMID:Performance characteristics of recombinant enzyme immunoassay to detect antibodies to human immunodeficiency virus type 1 (HIV-1) and HIV-2 and to measure early antibody responses in seroconverting patients. 881 30

Animal models of HIV-1 have a key role to play in elucidation of the cellular mechanisms responsible for protective immunity. Vaccination of domestic cats with whole inactivated feline immunodeficiency virus (FIV) elicits virus-neutralizing Abs and virus-specific CTL in the peripheral blood and lymphoid organs and affords protection from homologous virus challenge. In the present study we confirm the induction of virus-specific CTL following immunization with whole inactivated FIV vaccine and demonstrate that cats are protected for up to 1 yr following vaccination. Long term protection in vaccinated cats correlates with both higher levels of FIV Env-specific CTL in the peripheral blood following vaccination and the presence of FIV Env-specific memory CD8+ CTL in the lymph nodes, which persist for up to 1 yr following challenge in the absence of detectable virus. The CTL responses observed in vaccinated protected cats differ qualitatively from those in FIV-infected cats. The latter cats either do not generate a memory CTL response or exhibit a Gag-specific memory CTL response. These results show that the protective immunity observed in whole inactivated virus-vaccinated cats is associated with the induction of high levels of Env-specific CTL activity.
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PMID:Env-specific CTL predominate in cats protected from feline immunodeficiency virus infection by vaccination. 887 67

To study Mason-Pfizer monkey virus (MPMV) replication over a single round, virus particles were generated that contain a replication-defective vector encoding a dominant selectable marker, the hygromycin B phosphotransferase (hyg) gene. Genetic complementation with a homologous MPMV envelope glycoprotein (Env-gp) or pseudotyping by several heterologous Env-gps from a variety of viruses resulted in infectious MPMV particles containing the replication-defective RNA. Recently, it has been shown that human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) Rev and Rev-responsive element (RRE) functions can be substituted in vitro by a cis-acting sequence, the constitutive transport element (CTE), from simian type D retroviruses like MPMV and simian retrovirus type 1 (SRV-1). To determine whether CTE of MPMV is necessary for MPMV nucleic acid propagation, an MPMV vector that lacked the terminally located CTE was generated. Propagation of this vector was completely abrogated in the absence of CTE, showing the importance of CTE in MPMV replication. Insertion of CTE back into the MPMV genome in the sense orientation rescued replication to wild-type levels. Slot-blot analysis of nuclear versus cytoplasmic RNA fractions revealed that most of the messages were sequestered in the nucleus of cells transfected with the CTE(-) vectors and very little was transported to the cytoplasm. To test whether HIV-1 or SIV RREs could complement CTE function, the HIV-1 or SIV RREs were inserted in the CTE(-) vectors, trans complementation of CTE(-)RRE(+) vectors with Env-and Rev-expression plasmids rescued propagation of the CTE(-) vectors. Computer analysis predicted an RNA secondary structure in MPMV CTE analogous to the HIV-1 and SIV RREs that could form three stable stem loops, the first of which contains a site similar to the Rev-binding domain in the HIV-1 RRE. The presence of a higher-order CTE structure was analyzed by mutational analysis. We conclude that CTE is important in the replication of MPMV and affects the nucleocytoplasmic transport and/or stability of viral messages similar to the Rev/RRE regulatory system of HIV-1 and SIV.
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PMID:Role of Mason-Pfizer monkey virus (MPMV) constitutive transport element (CTE) in the propagation of MPMV vectors by genetic complementation using homologous/heterologous env genes. 887 12

We analysed clones of HeLa cells stably expressing the human immunodeficiency virus (HIV-1) envelope gene (env) and the HIV-1 receptor, CD4. Surprisingly, individual clones were found to consist of two distinct populations of cells differing by about 10-fold in the level of surface CD4. When high and low CD4-expressing cells were separated by FACS, each subpopulation gave rise to a mixture of high and low CD4-expressing cells after several days in culture. High and low CD4-expressing subpopulations did not differ with respect to the amount of intracellular Env, but there was an inverse correlation between CD4 and another HIV-1 protein encoded by the same segment of the HIV genome, Vpu. High surface CD4 cells had high levels of intracellular CD4, largely in the perinuclear region, and low levels of Vpu with a diffuse staining pattern. Conversely, low surface CD4 cells had low levels of intracellular CD4 with a diffuse staining pattern, and high levels of Vpu, largely in the perinuclear region. Vectors containing mutant versions of either Env or Vpu failed to down-regulate surface CD4. The phenomenon of bimodal expression of a surface protein in cells derived from single clones provides a simple model of differentiation in vitro. We show how a hypothetical interaction between CD4 and a multimer of Vpu, the multimerization of which is cooperative, would lead to bimodal expression of CD4. This model may be generalized and could explain other cellular 'switches'.
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PMID:Bimodal down-regulation of CD4 in cells expressing human immunodeficiency virus type 1 Vpu and Env. 888 70


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