Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant retroviral vectors can efficiently transduce and express foreign genes in mammalian cells. We have examined the utility of retroviral vector-mediated gene transfer to deliver genes which encode human immunodeficiency virus type I (HIV) antigens capable of stimulating specific immune responses. Murine fibroblast cell lines were transduced with a nonreplicating murine retroviral vector carrying the gene encoding the HIV-IIIB envelope protein and were shown to express the gp160/120 protein. Mice immunized with syngeneic vector-transduced cells developed CD8+, class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) specific for targets expressing the HIV envelope protein. The CTL also exhibited lytic activity on target cells coated with synthetic peptides derived from the gp120 V3 hypervariable region of both the HIV-IIIB and HIV(MN) isolates. Following adoptive transfer in a murine tumor model, these CTL were shown to be effective in vivo by their ability to eliminate established tumor cells expressing the HIV protein. Vector-transduced syngeneic cells were also capable of eliciting HIV envelope-specific antibody responses in immunized mice. Sera obtained from these mice were found to bind to the HIV-IIIB gp160 protein as well as a peptide-defined neutralizing antibody epitope contained within the V3 domain of gp120. These sera exhibited virus-neutralizing activity in that they markedly reduced the ability of HIV to infect and form syncytia of a human T-cell line. This is the first demonstration that cells transduced with a retroviral vector encoding the HIV-IIIB envelope protein are capable of inducing effective HIV-specific cellular and humoral immune responses in mice.
 ...
PMID:Induction of HIV-specific CTL and antibody responses in mice using retroviral vector-transduced cells. 193 Dec 34

This overview summarizes current knowledge on the overall efficacy and potential contribution of antibody-dependent cellular cytotoxicity (ADCC) and lymphokine-activated killer cell (LAK) activities in evoking non-major histocompatibility complex (non-MHC) cytolytic responses to human immunodeficiency virus-1 (HIV-1)-infected targets. High titers of ADCC antibodies to the HIV-1 virion are present in HIV-1-seropositive populations at all stages of disease. These antibodies are broadly reactive with a large number of HIV-1 strains and are predominantly directed against envelope determinants spanning both gp120 and gp41. However, the relative ability of natural killer (NK) effectors, derived from HIV-seropositive individuals, to evoke ADCC responses becomes increasingly impaired with disease progression. HIV-1-seropositive individuals also show marked decreases in both production of and responsiveness to interleukin-2 (IL-2). HIV-1-seropositive individuals generally have the ability to generate ex vivo propagated LAK cells; however, these cytolytic effectors are less effective than their counterparts derived from healthy controls. Increased understanding and control of non-MHC-restricted cytotoxic-responses to HIV, and their induction by lymphokines, may lead to improved treatment strategies for the management of AIDS and related diseases.
 ...
PMID:Role of antibody-dependent cellular cytotoxicity and lymphokine-activated killer cells in AIDS and related diseases. 194 Jun 15

The human CD4 molecule binds both human immunodeficiency virus envelope protein gp120 and class II major histocompatibility complex (MHC) molecules. We have studied a series of mutants in the region of amino acids 42-49 of CD4 for their ability to bind gp120, to interact with class II MHC, to enhance T-cell activation, and to bind a panel of anti-CD4 antibodies. The mutation Q40P (Gln40----Pro) and the deletion d42-49 were found to disrupt most antibody epitopes in the V1 domain of CD4, suggesting major conformational changes, whereas mutants F43L, G47R, and P48S retained the binding of most of the anti-CD4 antibodies tested. The mutants d42-49, Q40P, F43L, and G47R lost both gp120 and class II MHC binding as well as the ability to enhance T-cell activation. In contrast, the mutation P48S affected neither gp120 binding, nor class II MHC binding, nor T-cell activation. We conclude that within this region the binding sites for gp120 and for class II MHC molecules overlap and that amino acids Phe43 and Gly47 comprise an intimate part of both binding sites. These observations are consistent with a three-dimensional model of the V1 domain of CD4 that was developed in order to understand the structural basis for binding to CD4.
 ...
PMID:Identification and structural analysis of residues in the V1 region of CD4 involved in interaction with human immunodeficiency virus envelope glycoprotein gp120 and class II major histocompatibility complex molecules. 197 41

Several alleles at multiple HLA loci have been found to be associated with infection with human immunodeficiency virus (HIV): HLA A1; B8, B35; Cw7, Cw4; DR1, DR3 and DQ1, are associated with particular disease manifestations and/or disease progression. Furthermore, in a pilot study we have shown an increase in the frequency of C4 null alleles and suggested that all the reported HLA alleles could reflect association with a limited number of ancestral haplotypes (AHs). On this occasion, we studied 122 Caucasoid patients classified according to Centers for Disease Control (CDC) criteria. The control group consisted of 67 seronegative homosexual or bisexual males at risk of developing HIV infection. C4 null alleles were unequivocally present in 58% of patients in CDC IV compared with 33% of the seronegative subjects (chi 2 = 5.65, p less than 0.05). Furthermore, C4 null alleles could be excluded in only 8% and 16% of CDC III and IV, respectively, but in 30% of the seronegative subjects. An increased frequency of three AHs largely accounted for the increases in C4 null and HLA alleles. To examine the role of specific AHs we undertook a longitudinal analysis of a subgroup of 26 patients who seroconverted under observation. Seventeen of these patients were followed for 32 to 63 months. All seven patients with the 8.1 AH (A1, CW7, B8, BfS, C4AQ0, C4B1, DR3, DQ2) developed low CD4 lymphocyte counts (less than 450 x 10(6)/l) compared with only 2 of 10 patients without this haplotype (p less than 0.002). All three deaths occurred in patients with the 8.1 AH. The acquired immunodeficiency syndrome developed in three further cases with either 8.1- or B35-bearing (35.x) haplotypes. Sequential CD4/8 ratios showed an early and progressive decline in individuals with 8.1 or 35.x. Since the 8.1 and 35.x AHs contain deletions of the central major histocompatibility complex (MHC) genes, we suggest that the genes affecting HIV infection and progression are within the central MHC region.
 ...
PMID:Major histocompatibility complex genes influence the outcome of HIV infection. Ancestral haplotypes with C4 null alleles explain diverse HLA associations. 198 Oct 61

A variety of cellular proteins have been found to bind to related DNA sequences in the enhancer elements of the human immunodeficiency virus, the kappa immunoglobulin gene, the class I major histocompatibility complex gene, and the beta-interferon gene. Recently, lambda gt11 gene expression cloning using ligated oligonucleotide probes complementary to these DNA binding motifs has been performed. An identical cDNA clone encoding a cellular protein, referred to as HIV-EP1, MBP-1, or PRDII-BF1, that binds to each of these sequences has been identified. This cDNA potentially encodes a 298-kDa cellular protein with two widely separated zinc finger binding domains, each of which binds to the same DNA sequence. As part of an effort to examine the chromosomal organization of cellular genes encoding transcription factors, we report the chromosomal mapping of the gene encoding this zinc finger protein (ZNF40) to chromosome 6p22.3-24.
 ...
PMID:Localization of the zinc finger DNA-binding protein HIV-EP1/MBP-1/PRDII-BF1 to human chromosome 6p22.3-p24. 203

Simian immunodeficiency virus (SIV) gag-specific major histocompatibility complex (MHC)-restricted cytotoxic T-lymphocyte (CTL) activity was elicited in four out of six cynomolgus macaques after two immunizations with SIV gag recombinant vaccinia virus (rVV). No activity could be seen in three out of three non-immunized control animals. Low levels of anti-gag antibody were also seen in the same four responding animals. Virus-specific, MHC-restricted CTL are thought to give some protection and to assist in recovery in viral infection, and the induction of such CTL following vaccination with a single viral protein should act as an encouragement to those proposing similar vaccination studies in man.
 ...
PMID:Cytotoxic T-cell response to simian immunodeficiency virus by cynomolgus macaque monkeys immunized with recombinant vaccinia virus. 205 72

Infection by human immunodeficiency virus type-1 (HIV-1) is initiated when its envelope protein, gp120, binds to its receptor, the cell surface glycoprotein CD4. Small molecules, termed N-carbomethoxycarbonyl-prolyl-phenylalanyl benzyl esters (CPFs), blocked this binding. CPFs interacted with gp120 and did not interfere with the binding of CD4 to class II major histocompatibility complex molecules. One CPF isomer, CPF(DD), preserved CD4-dependent T cell function while inhibiting HIV-1 infection of H9 tumor cells and human T cells. Although the production of viral proteins in infected T cells is unaltered by CPF(DD), this compound prevents the spread of infection in an in vitro model system.
 ...
PMID:Prevention of HIV-1 infection and preservation of CD4 function by the binding of CPFs to gp120. 211 89

Highly purified, small dense splenic B cells from unstimulated mice showed increased expression of class II major histocompatibility complex (MHC) antigens and enhanced viability when cultured with affinity-purified recombinant interleukin 10 (rIL-10), compared with B cells cultured in medium alone. These responses were blocked by a monoclonal antibody (mAb) specific for IL-10, but not by an isotype-matched control antibody. IL-10 did not upregulate the expression of Fc epsilon receptors (CD23) or class I MHC antigens on small dense B cells or induce their replication as monitored by [3H]thymidine incorporation. While these B cell-stimulatory properties of IL-10 are also mediated by IL-4, the two cytokines appear to act independently in these assays; anti-IL-10 antibodies blocked IL-10 but not IL-4-mediated B cell viability enhancement, and vice versa. Similarly, since IL-4 upregulates CD23 on small dense B cells, the inability of IL-10 to do so argues against its acting via endogenously generated IL-4. Finally, IL-10 did not upregulate class II MHC antigens on B cells from X chromosome-linked immunodeficiency (XID) mice, while the same cells showed normal upregulation of class II antigens in response to IL-4. This report also extends our understanding of the relationship between IL-10 and the highly homologous Epstein-Barr virus (EBV)-encoded Bam HI fragment C rightward reading frame no. 1 (BCRFI) protein. It has previously been shown that BCRFI protein exhibits the cytokine synthesis inhibitory activity of IL-10. This report indicates that BCRFI protein also enhances in vitro B cell viability, but does not upregulate class II MHC antigens on B cells. One explanation for these data is that IL-10 contains at least two functional epitopes, only one of which has been conserved by EBV.
 ...
PMID:Interleukin 10, a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells. 212 52

Two broad roles have been revealed for the CD4 molecule. It serves as a receptor for both class II major histocompatibility complex molecules and human immunodeficiency virus (HIV). Upon binding class II major histocompatibility molecules, CD4 functions to enhance T-cell activation. By binding to CD4, HIV gains entry into the cell. We have used a chimeric molecule of CD4 and lymphocyte function-associated antigen 3 (LFA-3), CD4PI, which lacks a membrane-spanning domain and is instead anchored in the membrane by linkage to glycosyl-phosphatidylinositol. To further define the structural attributes of viral receptors, and specifically those of CD4 required for HIV infection, we have expressed CD4PI and CD4 in a human T-cell line, HSB-2. We find that CD4PI is able to mediate infection of these cells by HIV with similar, if not greater efficiency, compared with wild-type CD4. Thus the membrane-spanning region of CD4 is not required for HIV infection, and a lipid-anchored protein can serve as a viral receptor.
 ...
PMID:Human immunodeficiency virus infection is efficiently mediated by a glycolipid-anchored form of CD4. 214 6

We report that 11 human immunodeficiency virus 1 (HIV-1)-seropositive patients, including three AIDS patients, were able to generate a cellular immune response to the intradermal injection of low doses (2-10 micrograms) of recombinant interleukin 2 (rIL-2). A dose-dependent zone of induration appeared at the site of injection, peaked at 24 hr, and was accompanied by the local accumulation of T cells, monocytes, and Langerhans cells. Despite the reductions in the CD4+ T-cell counts in the peripheral blood of most patients, CD4+ T-cells could still be mobilized with rIL-2 injections into the skin. The total number of immigrant cells was equivalent to those in HIV-1-seronegative patients, although the CD4+/CD8+ ratio of the dermal population was reduced. In response to rIL-2, major histocompatibility complex (MHC) class II antigen was expressed on the surface of keratinocytes, Langerhans cells, lymphocytes, and macrophages. In addition, the gamma interferon (IFN-gamma)-induced protein IP-10 rapidly appeared in dermal inflammatory cells and keratinocytes. A majority of HIV-1-seropositive patients demonstrated low or absent responses to common skin-test antigens. Those with positive zones of induration were often defective in the cellular expression of the IFN-gamma-induced MHC class II antigen. The simultaneous administration of rIL-2 and soluble antigen at widely separated cutaneous sites led to an enhancement of skin-test antigen reactivity in seropositive patients. The results suggest that local administration of rIL-2 to seropositive patients may act systemically, stimulating cellular immunity to recall antigens, and thus may be of potential benefit in the defense against opportunistic pathogens encountered in HIV-1 infection.
 ...
PMID:Cutaneous response to recombinant interleukin 2 in human immunodeficiency virus 1-seropositive individuals. 214 21


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>