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)

Expression of the structural proteins of the human immunodeficiency virus type 1 (HIV-1), the human T-cell leukemia virus type I (HTLV-I), and of the transferrin receptor (TfR) mRNA depends on posttranscriptional regulatory mechanisms involving both positive and negative elements. In these systems the presence of elements decreasing mRNA expression have been demonstrated. The regulatory proteins (Rev, Rex or iron response element binding protein IRE-BP) antagonize the effects of the downregulatory elements by interacting directly with specific mRNA sites (Rev responsive element, RRE, Rex responsive element, RXRE, or iron responsive elements, IREs) resulting in stabilization and efficient expression of the corresponding mRNAs. To investigate whether this strategy involves common pathways of mRNA utilization, we have studied expression from hybrid mRNAs that contained these previously identified HIV-1 or TfR instability determinants and the binding sites of the regulatory proteins Rev, Rex and/or IRE-BP. Our results demonstrate that only low levels of these hybrid mRNAs accumulate in the absence of the positive regulatory factors Rev, Rex or IRE-BP. The presence of these factors counteracts the effect of heterologous downregulatory elements resulting in increased accumulation of the hybrid mRNAs. However, while Rev or Rex regulation also resulted in efficient protein expression, the IRE-BP only affected mRNA levels without significantly affecting protein expression, suggesting that the pathways of mRNA stabilization/expression are different in these systems.
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PMID:Rev of human immunodeficiency virus and Rex of the human T-cell leukemia virus type I can counteract an mRNA downregulatory element of the transferrin receptor mRNA. 798 24

Bacterial infections of the genital tract (gonorrhea, chlamydia, chancroid, syphilis) are common and cause significant morbidity. Their importance is heightened by recent appreciation of their roles in facilitation of transmission of the human immunodeficiency virus (HIV). Each is capable of causing repeated infections, suggesting lack of permanent broadly effective immunity. An effective vaccine has yet to be developed for any of these diseases. Rapid progress in understanding the molecular basis for pathogenesis of infection, including mechanisms for escape from otherwise effective immune surveillance and mechanisms for causing injury to host cells, has stimulated renewed efforts to make vaccines for some of these infections. Progress has been greatest for Neisseria gonorrhoeae and Chlamydia trachomatis. Present emphasis is on the major or principal outer membrane proteins of N. gonorrhoeae and C. trachomatis, based on evidence for neutralizing antibodies directed against surface-exposed variable domains of each of these proteins. Other surface-exposed proteins, including the iron-repressible transferrin receptor in gonococci and certain heat-shock proteins in chlamydia, also may be targets for vaccines. Although much remains to be learned, cautious optimism is warranted.
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PMID:Vaccines for bacterial sexually transmitted infections: a realistic goal? 814 39

Alveolar macrophages (AMs) harvested from 32 HIV-infected patients with respiratory problems (opportunistic pulmonary infections, n = 12; other lung disease, n = 20) and 13 healthy controls were stained with a panel of 15 monoclonal antibodies directed against surface antigens implicated in cell function. Antigen expression was quantified by flow cytometry and expressed as relative linear median fluorescence intensity (RLMFI). On AMs of patients, as compared with controls, there was a significant enhancement of HLA DP (12.1 +/- 1.5 vs 6.5 +/- 0.9, p = 0.01, M +/- SEM, RLMFI units), CD11b (3.4 +/- 0.5 vs 1.7 +/- 0.4, p = 0.014), CD11c (8.9 +/- 1.0 vs 4.8 +/- 0.8, p = 0.0046), CD14 (2.1 +/- 0.3 vs 1.0 +/- 0.2, p = 0.0009), and CD33 (1.7 +/- 0.1 vs 1.0 +/- 0.2, p = 0.0093). No significant differences could be established for HLA-DR (36.9 +/- 5.8 vs 30.9 +/- 7.5, NS), HLA-DQ (3.4 +/- 0.3 vs 3.1 +/- 0.6, NS), CD54 (1.9 +/- 0.3 vs 1.2 +/- 0.1, NS), CD13 (2.5 +/- 0.6 vs 1.5 +/- 0.3, NS), CD36 (1.4 +/- 0.2 vs 0.9 +/- 0.3, NS), CD71 (10.3 +/- 1.9 vs 8.9 +/- 1.8, NS), CD25 (0.8 +/- 0.0 vs 0.9 +/- 0.1, NS), 27E10 (1.1 +/- 0.1 vs 0.8 +/- 0.3, NS), RM3/1 (1.9 +/- 0.4 vs 1.5 +/- 0.4, NS), and CD4 (1.5 +/- 0.3 vs 1.0 +/- 0.0, NS). The expression of CD14 and CD11b, but not of HLA class II antigens and CD71, was increased in the smaller cell population compared with the larger, thus suggesting monocyte recruitment. The increased expression of HLA-DP, CD11c, CD14, and CD33 on the patients' AMs was independent of smoking habits. The degree of immunodeficiency as indicated by the absolute peripheral CD4 count, the character of HIV-related pulmonary disease, and the prophylactic use of pentamidine or zidovudine did not significantly modify the antigen expression pattern. It is concluded that HIV infection may lead, most probably indirectly, to enhanced expression of surface antigens by local upregulation and/or recruitment of monocytes from the peripheral circulation. The functional significance of enhanced marker expression requires further clarification.
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PMID:Expression of surface markers on alveolar macrophages from symptomatic patients with HIV infection as detected by flow cytometry. 818 14

High-grade B-cell-type non-Hodgkin's lymphomas are observed in 5% to 8% of patients positive for the human immunodeficiency virus. Nearly all cases belong to one of the three major histologic types: centroblastic or large noncleaved cell, immunoblastic and Burkitt's lymphoma, or small noncleaved cell. Some cases that are polymorphic are termed high-grade B-cell, not otherwise specified (NOS). The authors determined the immunophenotype of each histologic category of acquired immunodeficiency syndrome (AIDS)-related non-Hodgkins' lymphoma and sought a relationship with the presence of the Epstein-Barr virus (EBV). B-cell differentiation antigens, activation marker expression (human leukocyte antigen-DR, CD10, CD19, CD20, CD21, CD22, CD23, CD25, CD30, CD38), and epithelial membrane antigen were analyzed. The clonality was determined by the detection of cytoplasmic immunoglobulin, surface immunoglobulin, and the analysis of joining region (JH) immunoglobulin gene configuration by Southern blot. Epstein-Barr virus was detected either by Southern blot analysis using BamHI W probe fragment or by in situ hybridization with EBV-encoded RNA transcripts-1 specific probe. The immunophenotypic and genotypic results were compared with the morphology results and with the presence or absence of EBV. Burkitt's lymphomas were associated with EBV in 50% of cases, were monoclonal, and expressed mostly immunoglobulin (Ig) MK, CD10, CD19, CD20, CD22, and CD38. This immunophenotypic profile closely resembled those of the centroblastic cases (large noncleaved cell), in which EBV was absent. Epstein-Barr virus was associated with 90% of immunoblastic cases, and only CD10, CD20, and CD38 were expressed. CD71 was expressed in all categories of non-Hodgkin's lymphoma, and CD21 and CD23 were rarely expressed. Two cases of immunoblastic lymphoma and one case of high-grade B-NOS were polyclonal regarding JH rearrangement, but EBV tested with 1.9-Kb Xhol fragment was clonal. No significant immunophenotypic changes were noted in relation to the presence of EBV. Such studies comparing morphology, immunophenotype, and genotype could help classify and better understand the pathogenesis of AIDS-related non-Hodgkin's lymphoma.
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PMID:Immunophenotypic and genotypic analysis of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas. Correlation with histologic features in 36 cases. French Study Group of Pathology for HIV-Associated Tumors. 820 68

Prostaglandin E2 (PGE2) appears to have an immunosuppressive role in human immunodeficiency virus (HIV) infection. Therefore, the effect was studied of PGE2 pretreatment of T lymphocytes from patients with lymphadenopathy associated syndrome (LAS) on the expression of CD25 and CD71 as well as plaque forming cell (PFC) generation in pokeweed mitogen (PWM)-driven cultures. The PGE2-treated or untreated T lymphocytes were cultured with B cells and monocytes in the presence of PWM. Both CD25 and CD71 expression were assessed with an immunofluorescence technique; PFC generation was tested by hemolysis. Before exposure to PWM, LAS lymphocytes showed activation as evidenced by high CD25 and CD71 expression and PFC generation. Pretreatment by PGE2 did not inhibit expression of activation markers and PFC generation in LAS cultures, in contrast to what happened in control cultures. Thus, LAS lymphocytes are activated in vivo and are less sensitive to PGE2 inhibition than normal lymphocytes.
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PMID:Impairment of lymphocyte sensitivity to prostaglandin E2 in cultures from patients with lymphoadenopathy associated syndrome. 823 82

Anemia is responsible for an estimated 20% of maternal deaths in West Africa and contributes to still more deaths through obstetric hemorrhage. Anemia during pregnancy has been linked to iron and folate dietary deficiencies, the secondary effects of malaria and hookworm infestations, infections such as human immunodeficiency virus, and hemoglobinopathies. Parasitic infestations interfere with the normal increase (given a balanced diet) in iron absorption during pregnancy. An understanding of locally salient etiologic factors should form the basis of public health programs aimed at addressing anemia during pregnancy. There is a need for basic prevalence statistics, especially from West Africa's rural areas. Finally, reliable laboratory parameters that can be used in the assessment of iron and folate status and the degree of anemia attributable to malaria must be established. Although there is emerging evidence that serum transferrin receptor concentration is not affected by chronic disease or the physiological changes of pregnancy, further studies are needed to validate this measure.
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PMID:The aetiology of anaemia in pregnancy in West Africa. 913 12

The mechanisms involved in the incorporation of viral glycoproteins into virions are incompletely understood. For retroviruses, incorporation may involve interactions between the Gag proteins of these viruses and the cytoplasmic domains of the relevant envelope (Env) glycoproteins. Recent studies have identified within the cytoplasmic tail of the human immunodeficiency virus type 1 (HIV-1) Env protein a tyrosine-containing internalization motif similar to those found in the cytoplasmic domains of certain cell surface proteins that undergo rapid constitutive endocytosis in clathrin-coated pits. Given that surface expression of the HIV-1 Env protein is essential for the production of infectious virus, the presence of this internalization motif is surprising. We show here that in contrast to the rapid rate of Env protein internalization observed in cells expressing the Env protein in the absence of other HIV-1 proteins, the rate of internalization of Env protein from the surfaces of HIV-1-infected cells is extremely slow. The presence of the Pr55gag precursor protein is necessary and sufficient for inhibition of Env protein internalization, while a mutant Pr55-gag that is incapable of mediating Env incorporation into virions is also unable to inhibit endocytosis of the Env protein. The failure of the Env protein to undergo endocytosis from the surface of an HIV-1-infected cell may reflect the fact that the proposed interaction of the matrix domain of the Gag protein with Env during assembly prevents the interaction of Env with host adaptin molecules that recruit plasma membrane molecules such as the transferrin receptor into clathrin-coated pits. When the normal ratio of Gag and Env proteins in the infected cells is altered by overexpression of Env protein, this mechanism allows removal of excess Env protein from the cell surface. Taken together, these results suggest that a highly conserved system to reduce surface levels of the Env protein functions to remove Env protein that is not associated with Gag and that is therefore not destined for incorporation into virions. This mechanism for the regulation of surface levels of Env protein may protect infected cells from Env-dependent cytopathic effects or Env-specific immune responses.
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PMID:Human immunodeficiency virus type 1 envelope protein endocytosis mediated by a highly conserved intrinsic internalization signal in the cytoplasmic domain of gp41 is suppressed in the presence of the Pr55gag precursor protein. 879 89

Chemokines are chemotactic proteins which play a central role in immune and inflammatory responses. Chemokine receptors are members of the seven transmembrane G-protein coupled family and have recently been shown to be involved in the entry of human immunodeficiency virus (HIV) into target cells. To study chemokine endocytosis in detail we have used novel site-specific chemistry to make a fluorescently labeled CC-chemokine agonist (rhodamine-MIP-1alpha) and antagonist (NBD-RANTES). We have also generated a CHO cell line stably expressing a hemagglutinin-tagged version of the CC-chemokine receptor 1 (CCR1), and using these reagents we have examined the receptor-mediated endocytosis of CC-chemokines by confocal microscopy. Our studies reveal that the agonist was internalized and accumulated in transferrin receptor-positive endosomes whereas the antagonist failed to internalize. However, receptor-bound antagonist could be induced to internalize by co-administration of agonist. Analysis of receptor redistribution following chemokine addition confirmed that sequestration was induced by agonists but not by antagonists.
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PMID:Receptor-mediated endocytosis of CC-chemokines. 909 87

Varicella-zoster virus (VZV) encodes a cell surface Fc receptor, glycoprotein gE. VZV gE has previously been shown to display several features common to nonviral cell surface receptors. Most recently, VZV gE was reported to be tyrosine phosphorylated on a dimeric form (J. K. Olson, G. A. Bishop, and C. Grose, J. Virol. 71:110-119, 1997). Thereafter, attention focused on the ability of VZV gE to undergo receptor-mediated endocytosis. The current transient transfection studies demonstrated by confocal microscopy and internalization assays that VZV gE was endocytosed when expressed in HeLa cells. Endocytosis of gE was shown to be dependent on clathrin-coated vesicle formation within the cells. Subsequent colocalization studies showed that endocytosis of VZV gE closely mimicked endocytosis of the transferrin receptor. The gE cytoplasmic tail and more specifically tyrosine residue 582 were determined by mutagenesis studies to be important for efficient internalization of the protein; this tyrosine residue is part of a conserved YXXL motif. The amount of gE internalized at any given time reached a steady state of 32%. In addition, like the transferrin receptor, internalized gE recycled to the cell surface. The finding of gE endocytosis provided insight into earlier documentation of gE serine/threonine and tyrosine phosphorylation, since these phosphorylation events may serve as sorting signals for internalized receptors. Taken together with the previous discovery that both human and simian immunodeficiency virus envelope proteins can undergo endocytosis, the gE findings suggest that endocytosis of envelope components may be a posttranslational regulatory mechanism among divergent families of enveloped viruses.
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PMID:Endocytosis and recycling of varicella-zoster virus Fc receptor glycoprotein gE: internalization mediated by a YXXL motif in the cytoplasmic tail. 909 82

The sequence of events leading to clathrin-coated pit (CCP) nucleation on the cell surface and to the incorporation of receptors into these endocytic structures is still imperfectly understood. In particular, the question remains as to whether receptor tails initiate the assembly of the coat proteins or whether receptors migrate into preformed CCP. This question was approached through a dissection of the mechanisms implemented by Nef, an early protein of human and simian immunodeficiency virus (HIV and SIV, respectively), to accelerate the endocytosis of cluster of differentiation antigen type 4 (CD4), the major receptor for these viruses. Results collected showed that: (a) Nef promotes CD4 internalization via an increased association of CD4 with CCP; (b) the Nef-mediated increase of CD4 association with CCP is related to a doubling of the plasma membrane area occupied by clathrin-coated structures; (c) this increased CCP number at the plasma membrane has functional consequences preferentially on CD4 uptake and does not significantly affect transferrin receptor internalization or fluid-phase endocytosis; (d) the presence of a CD4 cytoplasmic tail including a critical dileucine motif is required to induce CCP formation via Nef; and (e) when directly anchored to the cytoplasmic side of the plasma membrane, Nef itself can promote CCP formation. Taken together, these observations lead us to propose that CD4 can promote CCP generation via the connector molecule Nef. In this model, Nef interacts on one side with CD4 through a dileucine-based motif present on CD4 cytoplasmic tail and on the other side with components of clathrin-coated surface domain (i.e., adaptins). These Nef-generated complexes would then initiate the nucleation of CCP.
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PMID:Nef-mediated clathrin-coated pit formation. 931 27


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