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

The interaction between the viral envelope protein gp120 and the cellular surface antigen CD4 is a key event in HIV-1 infection. Reciprocal high affinity binding sites have been located in the first domain of CD4 and in the carboxy-terminal region of gp120, respectively. Upon infection, the membranes of the target cells fuse; sites of CD4 and gp120, distinct from their high affinity binding sites, play a role in the post-binding events leading to syncytia formation. We have studied the interactions of CD4 with gp120 and gp120-derived peptides using an in vitro assay based on immobilized recombinant soluble CD4 (sCD4). In this system CD4 binds to recombinant soluble gp120 and to anti-receptor peptides derived from the high affinity CD4-binding site of gp120, as well as to peptides corresponding to the principal neutralizing domain (PND) of the envelope protein, i.e., to the domain required for HIV-1-mediated syncytium formation. Competition experiments performed using epitope-specific mAbs and a variety of peptides indicated that PND-derived peptides are specifically recognized by a CD4 site adjacent to, but distinct from, the high affinity gp120-binding site of CD4. Synthetic peptides patterned on the PND of different viral isolates were retained onto sCD4-based affinity columns at different extent; some of the structural requirements for binding were analyzed. Studies performed on CD4+ T-cells showed that PND-derived peptides also interact with CD4 in its native membrane-bound conformation. These results indicate that a direct contact takes place between CD4 and the gp120 domain participating in HIV-induced syncytia formation.
 ...
PMID:Binding to CD4 of synthetic peptides patterned on the principal neutralizing domain of the HIV-1 envelope protein. 172 May 90

The CD4 molecule is known to be the preferential receptor for the HIV-1 envelope glycoprotein. Epidermal Langerhans cells are dendritic cells which express several surface antigens, among them CD4 antigens. To clarify the exact role of CD4 molecules in Langerhans cell infection induced by HIV-1, we investigated the possible involvement of the interactions between HIV-1 gp 120 or HIV-1 gp 160s (soluble gp 160) and Langerhans cell surface. We also assessed the expression of CD4 molecules on Langerhans cell membranes dissociated by means of trypsin from their neighbouring keratinocytes. The cellular phenotype was monitored using flow cytometry and quantitative immunoelectron microscopy. We reported that human Langerhans cells can bind the viral envelope proteins (gp 120 or gp 160s), and that this binding does not depend on CD4 protein expression. This binding is not blocked by anti-CD4 monoclonal antibodies. We show that a proportion of gp 120/gp 160s-receptor complexes enters Langerhans cells by a process identified as a receptor-mediated endocytosis. The amount of surface bound gp 120/gp 160s is not consistent with the amount of CD4 antigens present on Langerhans cell membranes. Gp 120/gp 160s binding sites on Langerhans cell suspensions appeared to be trypsin resistant, while CD4 antigens (at least the epitopes known to bind the HIV-1) are trypsin sensitive. A burst of gp 120 receptor expression was detected on 1-day cultured Langerhans cells while CD4 antigens disappeared. These findings lead to the most logical conclusion that binding of gp 120/gp 160s is due to the presence of a Langerhans cell surface molecule different from CD4 antigens.
 ...
PMID:Interaction of human epidermal Langerhans cells with HIV-1 viral envelope proteins (gp 120 and gp 160s) involves a receptor-mediated endocytosis independent of the CD4 T4A epitope. 172 50

The human immunodeficiency virus (HIV-1) infects T lymphocytes via an interaction between the virus envelope glycoprotein gp120 and the CD4 antigen of T helper cells. Previous studies demonstrated that mutations in various regions of CD4 domain 1 lead to the loss of gp120 binding. In the present study the gp120 binding site was constructed in rat CD4 by replacing rat with human CD4 sequence. A series of mutants was constructed the best of which bound gp120 with an affinity only twofold less than that of human CD4. The data indicate that the gp120 binding site of human CD4 is constituted by residues 33-58 of domain 1.
 ...
PMID:Construction of a binding site for human immunodeficiency virus type 1 gp120 in rat CD4. 173 Sep 24

CD4 molecule, a surface marker of helper T lymphocytes, interacts with gp120 of human immunodeficiency virus (HIV) with a high affinity and, hence, serves as a virus receptor. Soluble chimeric CD4-immunoglobulin (Ig) possesses anti-HIV activity due to its binding activity to gp120. Furthermore, this recombinant molecule has unique Ig-like properties representing Fc receptor-binding activity and a long half-life in vivo. In this report we have thoroughly evaluated the effect of this compound on HIV infection using different in vitro systems. Treatment with 4 micrograms/ml of recombinant CD4-Ig after infection completely blocked the HIV-specific cytopathic effect, antigen expression, and virus release in MT-4 cells, a human T cell line which is highly susceptible to HIV. Similarly, this molecule blocked the HTLV-III/B and YU-1 strains of HIV infection in peripheral blood mononuclear cells even at 1 microgram/ml. Pretreatment of the Fc receptor-positive cell line U937 with this reagent resulted not in enhancement but again in blocking of HIV infection. About 95% of HIV infection was inhibited in U937 cells when cells were treated with this compound at the time of exposure to HIV. Recombinant-CD4-Ig also completely inhibited HIV-induced syncytia formation between MOLT-4 and MOLT-4/HIV and resulting virus release at 8 and 2 micrograms/ml, respectively. Due to its stability and long half-life, this compound could be a promising therapeutic agent against HIV infection.
 ...
PMID:Evaluation of anti-human immunodeficiency virus effect of recombinant CD4-immunoglobulin in vitro: a good candidate for AIDS treatment. 178 69

The ability of a variety of epithelial, embryonal, placental, and neuronal cells to express the CD4 antigen and to be infected by human immunodeficiency virus 1 (HIV-1) was examined. Only two (IMR-32 and HeLa-T4) expressed CD4 detectable by indirect immunofluorescence, and both were infectable by HIV-1. Two others, a human laryngeal carcinoma (HEp-2) and human colonic carcinoma (HT-29), did not express CD4 antigen but were infectable by HIV-1. Infection of the HEp-2 cells was detectable four months (and 20 serial passages) later. Infection of HEp-2 cells was not inhibited by anti CD4 monoclonal antibody but was by the lectin concanavalin A. These results suggest the presence of a receptor other than CD4 can be involved in HIV-1 infection.
 ...
PMID:Growth of human immunodeficiency virus I in cultured cells in the absence of the CD4 antigen. 180 30

A human Epstein-Barr virus-transformed B-cell line (IC.1) was characterized for cell surface antigen profile and permissivity to immunodeficiency virus (HIV) infection. According to cocultivation assay with MT2 cells, P24 release, and immunofluorescence assay, complement-sufficient serum enhanced in vitro infection of IC.1 cells. Enhancement occurs independently of the presence of HIV type 1-specific antibodies, although more efficiently when they are present. Blocking experiments with monoclonal antibodies demonstrated that complement receptor type 2 mediates this phenomenon and that the CD4 molecule is required for infection. Enhancement of in vitro infection on IC.1 cells appears closely related to previously described complement-mediated, antibody-dependent enhancement of HIV infection on the T-lymphoblastoid cell line MT2 (W. E. Robinson, Jr., D. C. Montefiori, and W. M. Mitchell, Lancet i:790-794, 1988).
 ...
PMID:Antibody-dependent and antibody-independent complement-mediated enhancement of human immunodeficiency virus type 1 infection in a human, Epstein-Barr virus-transformed B-lymphocytic cell line. 184 8

Immunohistological and electron microscopy studies of lymph nodes from patients infected with the human immunodeficiency virus 1 (HIV-1) demonstrated that follicular dendritic cells (FDC), the antigen-presenting cells of the B cell system, contain and may produce the virus. To elucidate the mode of infection of FDC with HIV-1 in vitro we developed an improved method for the preparation of single-cell suspensions of viable FDC with high purity (greater than 90% FDC). These isolated FDC were subjected to human T cell leukemia virus IIIB infection, which was monitored after 4 days in culture using the polymerase chain reaction. We were able to demonstrate that normal human FDC are highly susceptible to infection by HIV-1. Inhibition experiments with the monoclonal antibody OKT4a demonstrate that this infection is independent of the CD4 molecule.
 ...
PMID:Isolation of normal human follicular dendritic cells and CD4-independent in vitro infection by human immunodeficiency virus (HIV-1). 186 73

The CD4 molecule is known to be the preferential receptor for the HIV1 envelope glycoprotein. Epidermal Langerhans cells (LC) are dendritic cells which express several surface antigens, among them the CD4 antigens. LC infection was suggested when these cells were seen to present buddings coincident with membrane thickening of roughly 100 nm in size. These buddings were similar in ultrastructural aspect to HIV buddings on in vitro infected promonocytic cells (U937). To clarify the exact role of CD4 molecules in LC infection induced by HIV1, we investigated the possible involvement of between native and recombinant HIV1 gp120 and the LC surface. We also assessed the expression of CD4 molecules on LC membranes dissociated by means of trypsin from their neighbouring keratinocytes. The cellular phenotype was monitored using flow cytometry. We show that human LC can bind the viral envelope protein and that this binding does not depend on CD4 protein expression. The amount of surface bound gp120 was not consistent with the amount of CD4 antigens present on LC membranes. The gp120-binding sites on LC in suspension appear to be typsin-resistant while the CD4 antigens (at least the epitopes known to bind HIV1) are trypsin-sensitive. A burst of gp120 receptor expression was detected on 1-day cultured LC while the CD4 antigens disappeared. These findings lead to the logical conclusion that the binding of gp120 is due to the presence of a LC surface molecule which is different from CD4 antigens.
 ...
PMID:Trypsin-resistant gp120 receptors are upregulated on short-term cultured human epidermal Langerhans cells. 189 37

The envelope glycoprotein gp120 of primate immunodeficiency viruses initiates viral attachment to CD4+ cells by binding to the CD4 antigen on host cell surfaces. However, among different CD4+ cell types, different viruses display distinct host cell ranges and cytopathicities. Determinants for both of these biological properties have been mapped to the env gene. We have quantitatively compared the CD4 binding affinities of gp120 proteins from viruses exhibiting different host cell tropisms and cytopathicities. The viral proteins were produced by using a Drosophila cell expression system and were purified to greater than 90% homogeneity. Drosophila-produced gp120 from T-cell tropic human immunodeficiency virus type 1 (HIV-1) BH10 exhibits binding to soluble recombinant CD4 (sCD4) and syncytia inhibition potency identical to that of pure authentic viral gp120. Relative to the affinity of HIV-1 BH10 gp120 for sCD4, that of dual tropic HIV-1 Ba-L is 6-fold lower, that of restricted T-cell tropic simian immunodeficiency virus mac is 70-fold lower, and that of noncytopathic HIV-2 ST is greater than 280-fold lower. Thus, viruses that utilize CD4 for infection do so by using a remarkably wide range of envelope affinities. These differences in affinity may play a role in determining cell tropism and cytopathicity.
 ...
PMID:Envelope glycoproteins from biologically diverse isolates of immunodeficiency viruses have widely different affinities for CD4. 189 41

Benzylated peptides with a primary amino acid sequence corresponding to either human CD4(81-92) (#18), or chimpanzee CD4(81-92) (#18C), were equipotent inhibitors of human immunodeficiency virus type 1 (HIV-1) infection of CD4+ cells and high-affinity binding of 125I-gp120 to CD4+ cells. The chimpanzee-based CD4(81-92) peptide, however, which differs from the human peptide by a single amino acid substitution (E for G) at position 87, was considerably less potent than the human CD4(81-92)-based peptide congener to inhibit HIV-1-induced cell-cell fusion. These data suggest that a portion of the CD4 molecule contained within the sequence CD4(81-92) is involved in binding gp120 during both HIV-1 infection and HIV-1-induced syncytium formation in human cells, but that the presence of a glutamic acid at position 87 in this sequence is more critical for the CD4/gp120 interaction leading to syncytium formation than for the CD4/gp120 interaction leading to primary infection of CD4-positive cells. The region CD4(81-92) may critically contribute to CD4-mediated HIV-1 pathogenesis in humans, and its alteration might explain the lack of pathogenic sequelae of HIV-1 infection in chimpanzees.
 ...
PMID:Synthetic peptides allow discrimination of structural features of CD4(81-92) important for HIV-1 infection versus HIV-1-induced syncytium formation. 193 Dec 30


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