Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, epitopes of HIV envelope proteins that are involved in ADCC were identified. Peripheral blood mononuclear cells (PBMC) were obtained from adults with asymptomatic HIV infection or early symptoms of AIDS. These PBMC, which were reported to be "armed" in vivo with HIV-specific antibodies, were used as effector cells in 51Cr release assays. Target cells consisted of CD4 lymphocytes from healthy seronegative donors, coated with the IIIB strain of HIV-1 or with one of seven synthetic peptides. Cytotoxicity was detected against CD4 lymphocytes coated with HIV-1 IIIB or with the peptides env aa 507-518, corresponding to the carboxy-terminus of gp120, and env aa 597-611, corresponding to the region of the cysteine loop of gp41. The magnitude of target cell lysis was directly related to the quantity of peptide used. In contrast, target cells coated with the peptide gag aa 129-135, corresponding to the p17/p24 cleavage region of the gag precursor, were not killed. The same immunodominant regions which were involved in ADCC were recognized in enzyme-linked immunoabsorbent assays (ELISA) by the majority of 107 sera from HIV-infected adults. We conclude that the immunodominant epitopes located at the carboxy-terminus of gp120 and the cysteine loop of gp41 serve as recognition structure for antibodies, capable of mediating ADCC against HIV-infected cells.
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PMID:Antibody-dependent cellular cytotoxicity (ADCC) is directed against immunodominant epitopes of the envelope proteins of human immunodeficiency virus 1 (HIV-1). 128 12

Recombinant proteins derived from immunodominant conserved domains of HIV-1 env and gag genes were synthesized in E. coli. An immunoblot system using total cell lysates was employed for the analysis of recombinant bacterial clones. Together 427 serum samples obtained from asymptomatic anti-HIV seropositive individuals, AIDS patients, healthy donors and persons suffering from various conditions were comparatively evaluated for the presence of HIV-1 antibodies using recombinant peptides and commercially available western blot (WB) and ELISA assays. The recombinant antigen product of plasmid pEX41 was found to be superior, with respect to sensitivity and specificity, to the viral gp41 which represents a diagnostically important constituent of the WB.
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PMID:Bacterially expressed core and envelope proteins of human immunodeficiency virus type-1 (HIV-1): comparative evaluation in detection of type-specific antibodies. 128 76

In order to study SIV replication over a single round of replication virus particles were generated that contain a replication-defective vector containing a selectable marker. Genetic complementation between an env-deficient SIV variant and plasmid that expresses the env gene of an amphotropic murine retrovirus resulted in infectious SIV particles containing the vector. These pseudotyped particles exhibited an expanded host range through the use of an alternative receptor. This system should be useful in the genetic analysis of SIV nucleic acid replication. To determine whether the terminal cis acting components of the SIV genome might be sufficient for viral nucleic acid propagation a vector was generated which lack the internally located rev-responsive element. Propagation of this vector was reduced by at least 100-fold.
AIDS Res Hum Retroviruses 1992 Jan
PMID:Propagation of SIV vectors by genetic complementation with a heterologous env gene. 131 Jun 4

Serum samples collected from patients with a wide variety of diseases from African and other countries were tested for antibodies to the human spumaretrovirus (HSRV). A spumaviral env-specific ELISA was employed as screening test. Out of 3020 human sera screened, 106 were found to be positive (3.2%). While the majority of patients' sera from Europe (1581) were negative, 26 were positive (1.6%). Sera from healthy adult blood donors (609), from patients with multiple sclerosis (48), Graves' disease (45), and chronic fatigue syndrome (41) were negative or showed a very low prevalence for spumaviral env antibodies. A higher percentage of seropositives (6.3%) were found among 1338 African patients from Tanzania, Kenya, and Gabon. Out of 1180 patients from Tanzania, 708 suffered from tumors, 75 from AIDS, and 128 had gynecological problems; 51 of the Tanzanian patients were HSRV seropositive (4.3%). A particularly high percentage of 16.6% seropositives were identified among nasopharyngeal carcinoma patients (NPC) from Kenya and Tanzania consistent with results reported 10 years ago. However, 20 nasopharyngeal carcinoma patients from Malaysia were HSRV-seronegative. In selected cases, sera from seropositive individuals were reacted with proteins from HSRV-infected cells in vitro. HSRV env- and gag-specific antibodies were specifically detected by these sera in Western blots. The results indicate spumavirus infections in human patients with various diseases at a relatively low prevalence worldwide; in African patients, however, the prevalence of spumavirus infections is markedly higher.
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PMID:Human spumavirus antibodies in sera from African patients. 131 48

Maternal transmission of a murine leukemia virus (MuLV) mixture named LP-BM5 MuLV, which is knwon to induce murine AIDS (MAIDS), was investigated. Adult female C57BL/10 mice were inoculated intraperitoneally with LP-BM5 MuLV. When the virus-inoculated female mice developed splenomegaly or lymphadenopathy, they were mated with normal C57BL/10 male mice. Of 56 offspring born to MAIDS mothers, 14 appeared to develop MAIDS, as assessed by the occurrence of splenomegaly or lymphadenopathy as well as the mitogen response of spleen cells. The occurrence of MAIDS in offspring was found to be accompanied by the maternal transmission and expansion of a defective virus genome from which almost the entire pol and env regions are deleted. On the other hand, the ecotropic helper virus genome was detected in all offspring regardless of the occurrence of MAIDS. To examine the mode of maternal transmission of LP-BM5 MuLV, foster-nursing experiments were conducted. The ecotropic helper viruses were found in all normal offspring nursed by a MAIDS mother, and some of them developed MAIDS. In contrast, none of offspring born to a MAIDS mother that were nursed by an uninfected foster mother either carried the LP-BM5 MuLV or developed MAIDS. Finally, both the defective and the ecotropic helper viruses were detected in LP-BM5 MuLV-infected mother's milk. These results indicated that maternal transmission of LP-BM5 MuLV occurs with a high frequency and is mediated by mother's milk.
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PMID:High frequency of transmission of murine AIDS virus in C57BL/10 mice via mother's milk. 132 88

T cells in the peripheral blood are largely in the resting state and represent a significant pool of potential targets for HIV infection. The protection of these cells from infection is an important goal of nucleoside therapy. Resting PBL may not be protected effectively by such nucleosides as azidothymidine (AZT) since anabolic phosphorylation of thymidine nucleosides is reported to be limited in these cells. In this study we used DNA amplification procedures to follow HIV proviral DNA formation in resting T cells and to determine the ability of azidodeoxythymidine (AZT), dideoxyinosine (ddI), and dideoxycytosine (ddC) to inhibit this process. Experiments confirm that resting PBL synthesize HIV proviral DNA sequences. Drug titrations showed that this synthesis could be inhibited by nucleosides. ddC was the most potent drug, inhibiting transcription at the U5 region. ddI and AZT at similar concentrations (10 microM) did not inhibit. ddI in the concentration range of 10-100 microM was able to inhibit production of transcripts containing U3 and env sequences in resting cells. Similar inhibition levels were accomplished by AZT at 10-100-fold lower drug concentrations. These results demonstrate that resting T cells can be protected from HIV infection by nucleosides and that thymidine nucleosides are effective inhibitors despite the limited potential for anabolic phosphorylation.
AIDS Res Hum Retroviruses 1992 Jul
PMID:Inhibition of HIV infection of resting peripheral blood lymphocytes by nucleosides. 132 18

Feline immunodeficiency virus (FIV) has morphological, physical and biochemical characteristics similar to human immunodeficiency virus (HIV), the cause of AIDS in man. However, it is antigenically and genetically distinct from HIV; an antigenic relatedness with equine infectious anaemia virus has been demonstrated. FIV has been molecularly cloned and sequenced. Diagnostic tests are commercially available and attempts at preparing inactivated, subunit and molecularly engineered vaccines are being made in different laboratories. During FIV infection a transient primary illness can be recognized, with fever, neutropenia and lymphadenopathy. After a long period of clinical normalcy a secondary stage is distinguished with signs of an immunodeficiency-like syndrome. The incubation period for this stage can be as long as 5 years, during which gradual impairment of immune function develops. Many FIV-infected cats are presented for the first time showing vague signs of illness: recurrent fevers, emaciation, lack of appetite, lymphadenopathy, anaemia, leucopenia and behavioural changes. Later, the predominant clinical signs observed are chronic stomatitis/gingivitis, enteritis, upper respiratory tract infections, and infections of the skin. Neoplasias, neurological, immunological and haematological disorder are seen in a smaller proportion. The immunodeficiency-like syndrome is progressive over a period of months to years. Concomitant infection with feline leukaemia virus has been shown to accelerate the progression of disease. In vitro, phenotypic mixing between FIV and an endogenous feline oncovirus (RD114) has been demonstrated which leads to a broadening of the cell spectrum of the lentivirus. Bovine immunodeficiency virus (BIV) has been isolated only once, and all attempts to obtain additional isolates have failed; it has been recovered from the leucocytes of cattle with persistent lymphocytosis, lymphadenopathy, lesions in the central nervous system, progressive weakness and emaciation. As with the feline representative, BIV also was found to possess a lentivirus morphology and to encode a reverse transcriptase with Mg++ preference; it replicates and induces syncytia in a variety of embryonic bovine tissues in vitro. Antigenic analyses have demonstrated a conservation of epitopes between the major core protein of BIV and HIV. The original isolate has been molecularly cloned and sequenced. Besides the three large open reading frames (ORFs) comprising the gag, pol, and env genes common to all replication-competent retroviruses, five additional small ORFs were found. Numerous point mutations and deletions were found, mostly in the env-encoding ORF. These data suggest that, within a single virus isolate, BIV displays extensive genomic variation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Animal immunodeficiency viruses. 133 43

In vivo infection of monocytes/macrophages by the human immunodeficiency virus (HIV) has been investigated in many studies since these cells were suggested to provide a reservoir for the virus. In this study, we wanted to find out whether HIV provirus could be detected in circulating monocytes and whether it could be compared with the provirus found in T lymphocytes (T-Ly). Twenty-one seropositive subjects were studied. The amplification method (PCR) was used with three different primer pairs (in gag, env, and long terminal repeat regions of the viral genome) to detect the HIV-1 genome in monocytes and T-Ly separated by an immunomagnetic isolation technique. Of 21 monocyte samples, 13 (61.9%) were positive with at least one primer pair. Furthermore, the provirus harboured in 9 of those 13 monocyte-positive samples differed, with respect to pattern of primer response, from the provirus found in T-Ly. When comparing primer responses of monocytes and T-Ly, most of the differences were found to have occurred with the env primers (8 of 9 cases). Dilution experiments with the 8 E5 cell line revealed that 9 of 12 T-Ly contained 15-150 HIV DNA copies per 150,000 cells while 8 of 11 positive monocytes contained less than 15 copies. However, monocyte samples from two asymptomatic individuals and an AIDS patient showed high levels of HIV DNA, comparable to those obtained in T-Ly. Finally, it was also found that the monocyte-positive subjects were more immunosuppressed than the negative ones, as shown by the total CD4 count of both groups (means of 269 T4/mm3 and 573 T4/mm3, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
AIDS Res Hum Retroviruses 1992 Feb
PMID:HIV-1 in blood monocytes: frequency of detection of proviral DNA using PCR and comparison with the total CD4 count. 134 27

Candidate AIDS vaccines consisting of recombinant forms of the HIV-1 envelope glycoprotein induce, in seronegative human volunteers, an env-specific T cell response that includes CD4+, MHC class II-restricted CTL capable of lysing HIV-1-infected target cells. In this study, we have analyzed the production of the cytokines TNF-alpha and lymphotoxin (LT) by a set of env-specific CD4+ human CTL clones. TNF-alpha and LT are of interest because of their potential role in target cell destruction by CD4+ CTL. Our studies focused on the possibility that a cell surface form of TNF-alpha expressed by CTL after physiologic activation with target APC might participate in the cytolytic reactions mediated by these clones. We found that, upon interaction with target cells expressing env epitopes in the context of the appropriate MHC class II molecules, CD4+ CTL released TNF-alpha with kinetics that were rapid, compared with other cytokines, and that were generally similar to the kinetics of target cell destruction. LT secretion was not detected during the time course of the cytolytic reactions. A novel flow cytometric assay was used to show that physiologic activation of CD4+ CTL with target APC induced expression by the CTL of cell surface forms of TNF-alpha. Immunoprecipitations from activated, surface-iodinated CTL clones revealed two forms of surface TNF-alpha, a 26-kDa form, representing the transmembrane precursor of secreted TNF-alpha, as well as the 17-kDa secreted form bound to the cell surface. For a subset of CD4+ CTL, we found that treatment of CTL with cyclosporin A inhibited Ag-induced production of both transmembrane and secreted forms of TNF-alpha but had no effect on cytolysis. Thus, although transmembrane and secreted TNF-alpha produced by HIV-1-specific CD4+ CTL may have important effects in vivo, the rapid destruction of target APC by the set of CD4+ CTL clones described here occurs through a TNF-alpha-independent mechanism.
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PMID:Production of transmembrane and secreted forms of tumor necrosis factor (TNF)-alpha by HIV-1-specific CD4+ cytolytic T lymphocyte clones. Evidence for a TNF-alpha-independent cytolytic mechanism. 135 Oct 88

The antibody recognition of the major neutralization epitopes of human immunodeficiency virus type 1 (HIV-1) in 829 HIV-1-seropositive subjects from North America (106), Europe (241), Africa (342), and Asia (100) was investigated. Peptides derived from diverse published V3 loop sequences were used as antigen, and serum reactivity was detected by sensitive ELISAs. Antibody binding to peptides derived from the V3 loop sequence of HIV-1 isolates varies considerably depending on the geographic origin of the antibody and is associated with neutralization titer against homologous isolates. Serotype reactivity to peptides may be a simple and rapid approach to investigation of HIV-1 env diversity worldwide and may assist the choice of immunogen for development of future AIDS vaccines.
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PMID:Geographic diversity of human immunodeficiency virus type 1: serologic reactivity to env epitopes and relationship to neutralization. 137 May 25


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