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 primary cellular receptor for the human immunodeficiency viruses type 1 (HIV-1) and type 2 (HIV-2) is the CD4 antigen. HIV infection of CD4+ cells is initiated by binding of the virus to the cell surface, via a high affinity interaction between CD4 and the HIV outer envelope glycoprotein, gp120. The development of model systems using soluble recombinant forms of CD4 (sCD4) has allowed kinetic and thermodynamic analyses of CD4 binding to gp120, and study of the post-binding events leading to virus-cell membrane fusion. It has thus been demonstrated that the affinity of sCD4 for gp120 on virions or HIV-infected cells depends on both the primary sequence and the tertiary structure of gp120 in the membrane. With cell-line adapted isolates of HIV-1, sCD4 binding induces conformational changes in gp120, leading to the complete dissociation of gp120 from the transmembrane glycoprotein, gp41, and exposing cryptic epitopes of gp41. Similar observations have been made with cell-anchored CD4; exposure of cryptic gp41 epitopes occurs at the fusion interface between clusters of CD4-expressing and HIV-infected cells. Thus, for HIV-1, CD4 induces exposure of fusogenic components of gp41 which triggers virus-cell membrane coalescence. This is termed receptor-mediated activation of fusion. With primary isolates of HIV-1 and the related lentiviruses, HIV-2 and simian immunodeficiency virus (SIV), the CD4-induced molecular rearrangements in gp120 are more subtle, implying that there is a spectrum of responses to sCD4 binding. The high-affinity binding site on CD4 for gp120 is necessary and probably sufficient for activation of HIV fusion, although other regions of CD4 may indirectly influence viral entry. There are two regions on the envelope glycoproteins which are recognized as playing a role in HIV entry: the N-terminus of gp41 and the gp120 V3 loop. The roles of these domains are discussed.
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PMID:CD4 activation of HIV fusion. 128 Dec 2

The murine monoclonal antibody (MAb) 5A8, which is reactive with domain 2 of CD4, blocks human immunodeficiency virus type 1 (HIV-1) infection and syncytium formation of CD4+ cells (L. C. Burkly, D. Olson, R. Shapiro, G. Winkler, J. J. Rosa, D. W. Thomas, C. Williams, and P. Chisholm, J. Immunol., in press). Here we show that, in contrast to the CD4 domain 1 MAb 6H10, 5A8 and its Fab fragment do not block soluble CD4 (sCD4) binding to virions, whereas they do inhibit sCD4-induced exposure of cryptic epitopes on gp41 and dissociation of gp120 from virions. Two other MAbs, OKT4 and L120, which are reactive with domains 3 and 4 of CD4, have little or no effect on HIV-1 infection, syncytium formation, or sCD4-induced conformational changes in the envelope glycoproteins. The mechanisms of action of 5A8 and 6H10 can be further distinguished in syncytium inhibition assays: 6H10 blocks competitively, while 5A8 does not. We opine that 5A8 blocks HIV-1 infection and fusion by interfering with conformational changes in gp120/gp41 and/or CD4 that are necessary for virus-cell fusion.
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PMID:A monoclonal antibody to CD4 domain 2 blocks soluble CD4-induced conformational changes in the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and HIV-1 infection of CD4+ cells. 137 10

Human immunodeficiency virus (HIV) infects cells after binding of the viral envelope glycoprotein gp120 to the cell surface recognition marker CD4. gp120 is noncovalently associated with the HIV transmembrane envelope glycoprotein gp41, and this complex is believed responsible for the initial stages of HIV infection and cytopathic events in infected cells. Soluble constructs of CD4 that contain the gp120 binding site inhibit HIV infection in vitro. This is believed to occur by competitive inhibition of viral binding to cellular CD4. Here we suggest an alternative mechanism of viral inhibition by soluble CD4 proteins. We demonstrate biochemically and morphologically that following binding, the soluble CD4 proteins sT4, V1V2,DT, and V1[106] (amino acids 1-369, 1-183, and -2 to 106 of mature CD4) induced the release of gp120 from HIV-1 and HIV-1-infected cells. gp120 release was concentration-, time-, and temperature-dependent. The reaction was biphasic at 37 degrees C and did not take place at 4 degrees C, indicating that binding of soluble CD4 was not sufficient to release gp120. The appearance of free gp120 in the medium after incubation with sT4 correlated with a decrease in envelope glycoprotein spikes on virions and exposure of a previously cryptic epitope near the amino terminus of gp41 on virions and infected cells. The concentration of soluble CD4 proteins needed to induce the release of gp120 from virally infected cells also correlated with those required to inhibit HIV-mediated syncytium formation. These results suggest that soluble CD4 constructs may inactivate HIV by inducing the release of gp120. We propose that HIV envelope-mediated fusion is initiated following rearrangement and/or dissociation of gp120 from the gp120-gp41 complex upon binding to cellular CD4, thus exposing the fusion domain of gp41.
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PMID:Binding of soluble CD4 proteins to human immunodeficiency virus type 1 and infected cells induces release of envelope glycoprotein gp120. 200 55

Here we report the serological and immunochemical characterization of neutrophil-bound Ig (NBIg) and neutrophil-binding Ig in the serum of 15 individuals infected by the human immunodeficiency virus (HIV). We found no correlation between the presence or amount of NBIg or neutrophil-binding Ig in serum and either the serum concentration of IgG or the level of immune complexes (IC), as determined by the C1q-binding test. Twelve of the 15 eluates prepared from the neutrophils of the HIV-infected individuals reacted with donor neutrophils. These results indicate that NBIg in these men was not adhered IC nor passively absorbed Ig. This was supported by analysis of the sera of 13 of the 15 men by sucrose density-gradient centrifugation: neutrophil-binding Ig consisted predominantly of monomeric IgG. However, also low levels of IC capable of binding to neutrophils were detected in nine sera. Immunofluorescence studies revealed that neutrophil-binding Ig in the sera reacted with neutrophil-specific, non-polymorphic antigens that are not attached to the cell membrane via phosphatidyl-inositol linkage and, more specifically, not located on neutrophil FcRIII. None of the sera and eluates showed reactivity in the immunoprecipitation technique. Moreover, none of the eluates reacted with blotted neutrophil glycoproteins, whereas three sera reacted reproducibly and five sera reacted occasionally with a number of glycoproteins of different molecular weights in this technique. The latter results probably represent reactivity against cryptic and/or cytoplasmic antigens. Thus, NBIg in HIV infection has an autoantibody nature, but the full identity of the target antigens could not be clarified. These characteristics are not essentially different from those of the autoantibodies in classical autoimmune granulocytopenia.
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PMID:Neutrophil-bound immunoglobulin in HIV infection is of autoantibody nature. 201 67

A pneumococcal isolate that caused relapsing meningitis in a patient infected with human immunodeficiency virus (HIV) was found to display an unusual response to penicillin--rapid death but a striking lack of cellular lysis. This lytic defect was also detected in all four pneumococcal isolates from three additional HIV-infected patients and in more than half of the clinical isolates from patients with bacteremia. In a rabbit model of meningitis, the lysis-defective strain remained cryptic, with a delay of 5 h in the onset of leukocytosis in cerebrospinal fluid. A marked burst of leukocytosis was associated with ampicillin-induced lysis of a lysis-sensitive strain but not of a lysis-defective strain. Pneumococcal clinical isolates have different lytic responses to penicillin; defective lysis may adversely affect the course of meningitis, an observation suggesting that autolysins play a role in modulating infectious diseases.
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PMID:Microbiological and clinical significance of a new property of defective lysis in clinical strains of pneumococci. 339 19

Twenty-nine patients at risk of developing acquired immunodeficiency syndrome (AIDS) presented with cognitive, motor, and behavioral dysfunctions characteristic of the AIDS dementia complex, either preceding or in the absence of major systemic opportunistic infections or neoplasms. Six of these patients were medically well, while the remainder suffered only milder manifestations of the AIDS-related complex at the time of their neurologic presentation. Over half of these patients either survived for five to 16 months or died without exhibiting systemic manifestations of AIDS. This experience indicates that the AIDS dementia complex may be the earliest, and, at times, the only evidence of human immunodeficiency infection, and that its development in this context may present a diagnostic challenge, particularly in individuals in whom risk for infection by the AIDS virus is cryptic.
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PMID:The acquired immunodeficiency syndrome dementia complex as the presenting or sole manifestation of human immunodeficiency virus infection. 380 Jul 24

Neutralization of a chimeric human immunodeficiency virus (HIV) type 1, containing the V3 loop of the MN isolate substituted within the HXB2 envelope, was enhanced up to 20-fold compared with the HXB2 or MN parental isolates by human HIV-positive sera. MN V3 loop-specific monoclonal antibodies were better able to recognize the chimeric virus compared with MN, staining a greater percentage of infected cells and exhibiting slight increases in relative affinity with a concomitant increase in neutralization titer. Competition analysis revealed that enhanced neutralization by human HIV-positive sera of the chimera was attributable in some cases to better reactivity with the linear V3 loop epitope but in others to conformational loop epitopes or previously cryptic or poorly recognized epitopes outside the loop region. Mice primed with a vaccinia virus-chimeric envelope recombinant and boosted with gp160 developed a spectrum of antibodies different from that of mice similarly immunized with HXB2 or MN recombinants or that of naturally infected humans. The chimeric envelope elicited antibodies with enhanced binding to the native MN V3 loop; however, the sites seen by the BALB/c mice were not neutralizing epitopes. Nevertheless, similar to the observations made with use of human sera, the chimeric virus was more readily neutralized by all of the immune mouse sera, an effect apparently mediated by non-V3 loop epitopes. These studies illustrate that not only the V3 loop sequence and conformation but also its context within the viral envelope influence neutralization.
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PMID:Alteration of V3 loop context within the envelope of human immunodeficiency virus type 1 enhances neutralization. 751 75

The binding of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein, gp120, to its cell surface receptor, CD4, represents a molecular interaction involving distinct alterations in protein structure. Consequently, the pattern of epitopes presented on the gp120-CD4 complex should differ from those on free gp120. To investigate this concept, mice were immunized with covalently crosslinked complexes of viral HIV-1IIIBgp120 and soluble CD4. Two monoclonal antibodies (MoAbs) obtained from the immunized mice exhibited a novel epitope specificity. The MoAbs were marginally reactive with HIV-1IIIBgp120, highly reactive with gp120-CD4 complexes, and unreactive with soluble CD4. The same pattern of reactivity was seen in solid-phase assays using HIV-1(451)gp120. A similar specificity for complexes was evident in flow cytometry experiments, in which MoAb reactivity was dependent upon the attachment of gp120 to CD4-positive cells. In addition, MoAb reactivity was detected upon the interaction of CD4 receptors with purified HIV-1IIIB virions. Notably, seroantibodies from HIV-positive individuals competed for MoAb binding, indicating that the epitope is immunogenic in humans. The results demonstrated that crosslinked gp120-CD4 complexes elicit antibodies to cryptic gp120 epitopes that are exposed during infection in response to receptor binding. These findings may have important implications for the consideration of HIV envelope-receptor complexes as targets for virus neutralization.
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PMID:Monoclonal antibodies raised against covalently crosslinked complexes of human immunodeficiency virus type 1 gp120 and CD4 receptor identify a novel complex-dependent epitope on gp 120. 754 51

Rhodococcus equi is an emerging opportunistic pathogen of human immunodeficiency virus-infected patients. However, little is known about the characteristics of R. equi isolates from humans. This study characterized the plasmid content, expression of a virulence-associated antigen, and mouse virulence of 19 R. equi isolates from patients with and without AIDS. EcoRI digestion patterns and Southern, Western, and virulence analyses of these isolates with cryptic plasmids allowed definition of a new category of R. equi. Isolates from patients with AIDS tended either to be virulent and have 15- to 17-kDa antigens and an 85-kb plasmid (10(6) bacteria needed for lethality) or have intermediate virulence (10(7) bacteria needed for lethality) and one of four distinct large plasmids that share DNA homology and express a 20-kDa antigen. Most of the non-AIDS isolates were avirulent (> 10(8) bacteria needed for lethality) and did not express any of these antigens.
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PMID:Identification of virulence-associated antigens and plasmids in Rhodococcus equi from patients with AIDS. 759 68

A panel of six IgG monoclonal antibodies (MAbs) was produced by immunizing mice with a 22 amino acid synthetic peptide, designated V3.3, of the third variable region of feline immunodeficiency virus (FIV) envelope glycoprotein. This peptide is known to induce neutralizing antibodies in cats. In ELISA all MAbs reacted with purified SDS-disrupted FIV and in flow cytometry all MAbs stained permeated, persistently infected FL4 cells but not unfixed FL4 cells; this indicated that the MAbs recognize essentially cryptic epitopes of the gp100 V3 loop. By direct ELISA using partially overlapping synthetic peptides and by competition binding studies, the anti-V3.3 MAbs were shown to detect at least four distinct epitopes, two located in the amino-terminal half and two in the carboxy-terminal half of the sequence. When tested for neutralizing activity by the syncytium inhibition assay in Crandell feline kidney cells, all anti-V3.3 MAbs neutralized FIV at high dilution. However, at low dilution two MAbs exhibited much less neutralizing activity. These results indicate that the V3 region of FIV contains multiple epitopes involved in neutralization.
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PMID:Epitope mapping of the V3 domain of feline immunodeficiency virus envelope glycoprotein by monoclonal antibodies. 763 70


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