Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antigens in a particulate conformation were shown to be highly immunogenic in mammals. For this reason, the particle forming capacity of derivatives of the HIV-1 group specific core antigen p55 gag was assayed and compared dependent on various expression systems: recombinant bacteria, vaccinia- and baculoviruses were established encoding the entire core protein p55 either in its authentic sequence or lacking the myristylation consensus signal. Moreover, p55 gag was expressed in combination with the protease (p55-PR) or with the entire polymerase (p55-pol), respectively. Budding of 100-160 nm p55 core particles, resembling immature HIV-virions, was observed in the eucaryotic expression systems only. In comparison to the vaccinia virus driven expression of p55 in mammalian cells, considerably higher yields of particulate core antigen were obtained by infection of Spodoptera frugiperda (Sf9) insect cells with the recombinant Autographa californica nuclear polyhedrosis (AcMNPV) baculovirus. Mutation of the NH2-terminal myristylation signal sequence prevented budding of the immature core particles. Expression of the HIV p55-PR gene construct by recombinant baculovirus resulted in complete processing of the p55 gag precursor molecule in this system. The introduction of an artificial frameshift near the natural frameshift site resulted in constitutive expression of the viral protease and complete processing of p55, both in Escherichia coli and in vaccinia virus infected cells. Interestingly, significant processing of p55 resembling that of HIV infected H9 cells could also be achieved in the vaccinia system by fusing the entire pol gene to the gag gene. Moreover, processing was not found to be dependent on amino-terminal myristylation of the gag procursor molecule, which is in contrast to observations with type C and type D retrovirus. However, complete processing of p55 into p24, p17, p9 and p6 abolished particle formation. Purified immature HIV-virus like particles were highly immunogenic in rabbits, leading to a strong humoral immune response after immunization. Empty immature p55 gag particles represent a noninfectious and attractive candidate for a basic vaccine component.
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PMID:Studies on processing, particle formation, and immunogenicity of the HIV-1 gag gene product: a possible component of a HIV vaccine. 145 88

The analysis of human immunodeficiency virus type 1 (HIV-1) RNA sequences in CEM and Jurkat lymphoid cells infected with the virus has been performed at the subcellular level. Using a biotinylated DNA probe specific for HIV-1, virus RNA sequences were detected on Lowicryl thin sections after immunogold cytochemistry. The labelling observed on the cytoplasm was localized near the plasma membrane connected with extracellular cluster of virions. On free immature and nascent form of the virus the detection of HIV-1 RNA was associated with the peripheral electron-dense structure, whereas on mature form the labelling was concentrated on the central nucleoid known to be the site of the HIV-1 genomic RNA. The identification of virus RNA was also performed simultaneously with the detection of HIV-1 core protein p24 or p17 using a double immunogold labelling. Whereas the HIV-1 RNA showed again a cytoplasmic and virions localization, the structural protein was only observed on viral formations. The cytoplasmic localization of virus RNA, at the time of virus production, suggests that they are of genomic origin destined to be packaged in virions once the assembly of virus structural proteins has taken place in the plasma membrane at the viral budding site. The present molecular investigation conducted at the subcellular level provides insight into the cell periphery distribution of HIV-1 RNA observed at the light microscope as corresponding to the detection of HIV-1 infected lymphoid cells actually releasing virions.
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PMID:Ultrastructural localization of HIV-1 RNA and core proteins. Simultaneous visualization using double immunogold labelling after in situ hybridization and immunocytochemistry. 145 33

Rectal mucosal biopsy specimens from 75 human immunodeficiency virus (HIV)-seropositive and 16 HIV-seronegative subjects were examined. The histopathologic changes were correlated with immunoperoxidase staining for UCHL-1 and HIV core protein p24, quantitative p24 enzyme-linked immunosorbent assay (ELISA) assay in homogenized rectal tissue and serum, and a modified Walter Reed clinical stage. Four phases were seen in the HIV-infected subjects: (1) early phase, in Walter Reed stage 1-2 subjects, with nearly normal histology and low p24; (2) inflammatory phase, typically in Walter Reed stage 3-4 subjects, with a superficial lamina propria infiltrate of lymphocytes, plasma cells, and eosinophils with degranulation, abundant UCHL-1 staining, and maximal p24 by both immunoperoxidase staining and ELISA; (3) transitional phase, in many Walter Reed 5 and some Walter Reed 6 subjects, with normal lymphocyte population density but with subtle inflammatory changes; and (4) lymphoid depletion phase, mainly in Walter Reed stage 6 subjects, with decreased lymphocytes but often with endothelial cell activation and apoptosis. These phases presumably result from effective HIV suppression by a relatively intact immune system, followed by maximal HIV infection and lymphocyte activation, then progressive lymphocyte depletion. The inflammation correlated with the presence and amount of HIV in rectal tissue determined by immunohistochemistry and ELISA and was maximal before overt immunodeficiency developed. Intestinal mucosa could be a preferred site of HIV proliferation and T-cell destruction.
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PMID:Rectal mucosal pathology varies with human immunodeficiency virus antigen content and disease stage. 149 43

Polyadenylic-polyuridylic acid referred to as poly(A).poly(U) is a synthetic double-stranded RNA which has been shown to manifest both antitumoral and immunomodulatory activities. Here we used this agent to demonstrate its antiviral activity against the human immunodeficiency virus (HIV-1 and HIV-2). Treatment of cells with poly(A).poly(U) resulted in a significant delay in the development of the HIV-specific cytopathic effect characterized by the formation of syncytia and cell lysis. Furthermore, the production of virus measured by the concentration of the HIV major core protein was reduced by 90-95%. Under these experimental conditions, the synthesis of HIV proteins was reduced at least tenfold whereas the metabolism and proliferation of cells apparently were not affected. The inhibitory action of poly(A).poly(U) seems to be at the level of viral entry into cells. Combined treatment of infected cells with poly(A).poly(U) and azidothymidine (AZT) resulted in a 4-5-fold synergistic inhibitory effect. Previously, no toxicity has been observed in cancer patients with long-term treatment with poly(A).poly(U). In view of this and the significant anti-HIV effect, poly(A).poly(U) provides a potential candidate as a therapeutic drug in AIDS disease.
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PMID:Antiviral action of polyadenylic-polyuridylic acid against HIV in cell cultures. 154 Apr 14

Seventy infants born to human immunodeficiency virus type 1 (HIV-1) seropositive mothers were studied for specific antibody (IgA, IgM and IgG) production and the presence of active infection (detectable level of virus in peripheral blood lymphocytes). Among these children, followed for up to 15-40 months after birth, 11 presented unequivocal signs of HIV-1 infection (persistent p24 antigenemia and/or positive virus isolation). Analysis of sera by immunoblotting showed that IgA antibody to HIV-1 p24 core protein, alone or associated with envelope glycoproteins (gp120, gp41), was present in the majority of infected babies (7 of 11), while IgM was found in a lower percentage of cases (4 of 11). No IgA and or IgM antibody to HIV-1 was ever found in babies, born to seropositive mothers, who seroreverted after birth or in the control group enrolled in this study. Our results indicate that immunoblotting analysis of IgA antibody to HIV-1 polypeptides may represent a useful complementary prognostic marker in children born to HIV-1 seropositive mothers.
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PMID:Immunoblotting analysis of IgA and IgM antibody to human immunodeficiency virus type 1 (HIV-1) polypeptides in seropositive infants. 156 80

The nucleotide sequence of a murine monoclonal antibody (CB-mab-p24/13-5) against p24 core protein of the human immunodeficiency virus (HIV-1) was determined for variable regions of the heavy and light chain, respectively. Genetic elements encoding the VDJH- and VJL-regions of the antibody were generated from RNA by the polymerase chain reaction, cloned into the vector pICEM 19R and sequenced. Synthetic peptides, 10 amino acids overlapping served for the localization of the epitope. The residues 152-156 within the p24 sequence contain the epitope.
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PMID:Immunoglobulin V regions and epitope mapping of a murine monoclonal antibody against p24 core protein of HIV-1. 156 2

In mice experimentally infected with 1 x 10(5) UI/mouse of HTLV-IIIB IgM antibodies were detected 10-12 days after the infection, reaching peak values two weeks later; the IgM seratiter progressively decreased thereafter and was negative at ten-eleven weeks. HIV p24 antigen was detected ten-fifteen days after infection and reached peak values five-six weeks later. Antigenemia subsequently decreased and showed an oscillating course with a progressive decrease which persisted throughout the observation period. Two weeks after infection we detected IgG antibodies to the major core protein p24; reactivity to gp41 was observed as early as reactivity to p24 and persisted throughout observation period. The IgG antibodies to all HIV epitopes peaked two-three weeks after infection; the time course showed a decrease after ten weeks, progressively decreasing thereafter. After sixty-five weeks of infection the IgG seratiter value was lower but remained positive. Viruses indistinguishable from HIV were isolated from the peripheral blood mononuclear cells of infected mice 30, 60, 180 days after infection. These seroimmunological and virological data confirm that the immunocompetent mouse may serve as a low-cost reproducible model for HIV-1 in vivo research.
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PMID:Mice infection with HIV-1: a new mouse model for HIV-1 in vivo research. 160 87

Murine monoclonal antibodies (Mabs) to the major core protein p24 of the human immunodeficiency virus type 1 (HIV-1) were tested for their ability to inhibit the replication and spread of the virus in permanent cell cultures (Molt4/8, K37, H9) and in the culture of II-2 stimulated T cells of healthy donors. After addition of ascitic fluid containing monoclonal anti-p24 antibodies or purified anti-p24 antibodies or the respective control to co-cultures of infected and non-infected cells, HIV-1 replication was evaluated by determining the percentage of infected cells and the activity of reverse transcriptase (RT) in cell-free supernatant. In addition, the supernatant's infectivity was determined. FACS analysis demonstrated p24 antigen in about 40% of unfixed HIV-1 infected cells at the cell membrane. Monoclonal anti-p24 antibodies of different epitope specificity added to the cells but not to the virus delayed the spread of HIV-1 infection in permanent cell culture. Furthermore, anti-p24 Mabs inhibited the release of RT-active virus particles by HIV-1 infected cell lines or II-2 stimulated T-lymphocytes, respectively, up to 60%. The mode of action of anti-p24 antibodies after HIV-1 infection is discussed on the basis of the data obtained.
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PMID:Inhibition of HIV-1 infection in vitro by murine monoclonal anti-p24 antibodies. 162 12

A study was conducted to assess the relative contribution of the HIV-1-specific immune response and -nonspecific immune activation to HIV disease progression. The titer of antibody to the p24 core protein and the concentration of serum neopterin were measured in 238 HIV-1-seropositive subjects in a prospective cohort study of homosexual men. Antibody titers were extremely variable among cohort participants but relatively stable over time, suggesting inherent differences in the initial immune response capacity. Neopterin concentrations were also variable at cohort entry but generally increased over time. These two markers, measured at cohort entry, had powerful and independent predictive value for the development of AIDS up to 54 months before diagnosis. Subjects with low antibody titers and high levels of neopterin, had the highest incidence of AIDS (60% over 54 months). Patients with low antibody or high neopterin alone had an intermediate risk (34% incidence) and less than 10% of those with high antibody and low neopterin developed AIDS. We propose that the initial immune response to HIV and virus-mediated immune system activation are independent and innately variable components of an individual's response to HIV infection that interact to determine the clinical outcome.
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PMID:The initial immune response to HIV and immune system activation determine the outcome of HIV disease. 167 78

We have investigated Th cell recognition of the HIV core protein p24 by using CD4+ T cell clones derived from cynomolgus macaques immunized with hybrid HIV p24: Ty virus-like particles (VLP). T cell lines from two immunized animals responded to p24: Ty-VLP, control Ty-VLP, purified p24, and whole inactivated HIV, indicating the presence of T cells specific for p24 as well as the Ty carrier protein. The HIV determinants recognized by the T cell lines were identified by using a series of overlapping peptides synthesized according to the sequence of p24. Both T cell lines recognized peptide 11 (amino acids 235-249) and peptide 14 (amino acids 265-279). In addition, one T cell line also responded to peptide 9 (amino acids 215-229). Definitive identification of two T cell epitopes on p24 was confirmed at the clonal level: from a total of four T cell clones generated from one of the T cell lines, two respond specifically to peptide 11 and two to peptide 14. The T cell clones were CD4+ and MHC class II-restricted and secreted IL-2 in response to stimulation with purified p24, inactivated HIV or a single synthetic peptide. The specificity of the Th clones for variant peptides demonstrated cross-reactivity with two simian immunodeficiency virus isolates, but only limited responses to HIV-2 sequences. However, the Th cell epitopes identified on p24 are highly conserved between 12 HIV-1 isolates and were recognized by both of the immunized primates. These sequences may therefore be useful for priming a broadly reactive immune response to HIV-1.
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PMID:HIV p24-specific helper T cell clones from immunized primates recognize highly conserved regions of HIV-1. 168 53


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