Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 gene encoding the 856-amino-acid envelope glycoprotein, gp160, of human immunodeficiency virus type 1 was mutagenized and transfected into Chinese hamster ovary cells. Continuous cell lines that constitutively produced gp160 variants were isolated and used to study the biosynthesis and orientation of gp160 in cellular membranes. In vivo studies of gp160 variants failed to reveal domains upstream of amino acid residue 665 that could serve as stop transfer sequences. Analyses of gp160 variants expressed in vitro in a translation-coupled translocation system were consistent with the in vivo studies and provided evidence that gp160 is a simple bitopic membrane protein. A model for the orientation and function of gp160 in cellular membranes is presented. The cell lines described provide a convenient source of the gp120-gp41 complex.
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PMID:Expression of membrane-associated and secreted variants of gp160 of human immunodeficiency virus type 1 in vitro and in continuous cell lines. 284 66

Derivatives of the CEM T and WIL-2 B cell lines showed striking diversity in their responses to the HTLV-IIIB strain of the human immunodeficiency virus (HIV). Several stable phenotypic patterns could be defined, based on whether cells were permissive (P+, P-) for virus production, were sensitive or insensitive to cytopathic effects after infection by free virus (C+, C-), and whether they underwent fusion on contact with virus-infected cells (F+, F-). Although expression of CD4 was essential for infection by HTLV-IIIB, very low levels were sufficient for productive infection of WIL-2 derivatives. Conversely, some CEM T cell lines that expressed ample CD4, and which were able to bind virus gp120 and undergo fusion, did not support productive infection by free virus. One nonpermissive, CD4+ derivative of CEM could bind gp120 but failed to undergo fusion, suggesting an alteration in some membrane protein other than CD4 that is essential for virus entry and HIV-induced cell fusion. The AA2 derivative of the WIL-2 cell line is also described, which is remarkably permissive for HIV replication and exquisitely sensitive to virus cytopathic effect. The panel of related cell lines with different host-virus phenotypes could be useful for more precisely defining steps in the infectious cycle of HIV, and for identifying host cell genes and gene products that determine the outcome of HIV infection.
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PMID:Phenotypic variation in the response to the human immunodeficiency virus among derivatives of the CEM T and WIL-2 B cell lines. 326 75

The stability of potential RNA stem-loop structures in human immunodeficiency virus isolates, HTLV-III and ARV, has been calculated, and the relevance to the local significant secondary structures in the sequence has been tested statistically using a Monte Carlo simulation method. Potentially significant structures exist in the 5'non-coding region, the boundary regions between the protein coding frames, and the 3' non-coding region. The locally optimal secondary structure occurring in the 5' terminal region has been assessed using different overlapping segment sizes and the Monte Carlo method. The results show that the most favorable structure for the 5' mRNA leader sequence of HIV has two stem-loops folded at nucleotides 5-104 in the R region (stem-loop I, 5-54 and stem-loop II, 58-104). A large fluctuation of segment score of the local optimal secondary structure also occurs in the boundary between the exterior glycosylated protein or outer membrane protein and transmembrane protein coding region. This finding is surprising since no RNA signals or RNA processing are expected to occur at this site. In addition, regions of the genome predicted to have significantly more open structure at the RNA level correlate closely with hypervariable sites found in these viral genomes. The possible importance of local secondary structure to the biological function of the human immunodeficiency virus genome is discussed.
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PMID:Stability of RNA stem-loop structure and distribution of non-random structure in the human immunodeficiency virus (HIV-I). 338 21

CD4 is the predominant cell membrane protein that binds human immunodeficiency virus type 1 (HIV-1) gp120 and facilitates HIV-1 infection, but other membrane-associated molecules may be involved in determining HIV-1 cellular infection. Our prior work had suggested that CD44, the transmembrane receptor for hyaluronan, might play a role in the infection of mononuclear phagocytes with HIV-1. In the present work, we have used cells of the CD4-positive, CD44-negative human T-lymphoblast cell line Jurkat to study the role of CD44 in HIV-1 infection and tropism. Cells were transfected with cDNA for the standard (S, or hematopoietic) CD44 isoform CD44S or the epithelial isoform CD44E. The resultant lines expressed appropriate CD44S or CD44E mRNA and protein. While the parent Jurkat cells, those transfected with vector alone, and those transfected with CD44E could be productively infected with only the lymphocytotropic strain HIV-1-LAI, cells transfected with CD44S were rendered susceptible to productive infection with the monocytotropic strains HIV-1-BaL and HIV-1-ADA. Also, CD44S-transfected cells displayed higher levels of infection with HIV-1-LAI than did the other transfected Jurkat cells. The transfected cell line cells all had comparable growth rates and expressed similar levels of the membrane antigens CD4, CD7, major histocompatibility complex (MHC) class I, MHC class II, and CD11a, while levels of CD3 were slightly higher in cells transfected with vector alone and in one of the clones transfected with CD44S. Hyaluronan binding was increased in cells transfected with either CD44S or CD44E. Mouse NIH 3T3 fibroblasts transfected with human CD4, human CD44S, or both human CD4 and CD44S displayed the appropriate antigens, but they could not be productively infected with lymphocytotropic or monocytotropic strains of HIV-1. The results indicate that in human leukocytes, CD44S is an important determinant of HIV-1 productive infection and may be involved in viral cellular tropism.
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PMID:Cellular CD44S as a determinant of human immunodeficiency virus type 1 infection and cellular tropism. 753 3

Severe immunodeficiency is associated with reactivation of latent Epstein-Barr virus (EBV) that is manifested by virus replication. It is unknown whether EBV replication also occurs in the Hodgkin's disease (HD) tissue of patients infected with the human immunodeficiency virus (HIV). Therefore, we studied paraffin-embedded lymph nodes from 13 cases of HIV-associated HD to determine the latent or replicative state of EBV infection. All patients were seropositive HIV-infected men; additional clinical information was available for 12 patients. The risk factor(s) for HIV infection were homosexuality (n = 7), intravenous drug abuse (n = 2), homosexuality and intravenous drug abuse (n = 1), sexual promiscuity (n = 1), or hemophilia (n = 1). Advanced clinical stage and B symptoms were common at the time of initial diagnosis of HD. The histological subtype of Hodgkin's disease was universally mixed cellularity, except for a single case classified as nodular sclerosis. Seven cases exhibited foci of relative lymphoid depletion. Five cases contained foci of necrosis. Reed-Sternberg (RS) cells and RS cell variants were positive for CD30/BerH2 and negative for CD45/LCA, CD45RO/UCHL1, and CD20/L26 in all cases. Tumor cells were positive for CD15/LeuM1 in seven cases. In all 13 cases, RS cells and RS cell variants were infected by latent EBV as shown by in situ hybridization to EBV-encoded ribonucleic acid (EBER1). In 12 of 13 cases neoplastic cells coexpressed EBV latent membrane protein 1 (LMP1). EBV replication was examined by two different methods: immunohistochemistry to identify EBV-encoded BZLF1 protein and in situ hybridization to detect EBV BHLF1 transcripts. No positivity in RS or RS cell variants was detected with either assay of EBV replication (95% confidence interval [CI] = 0% to 23%). The findings confirm that EBV is detected more frequently in HIV-associated HD when compared with immunocompetent patients with HD. The findings also suggest that EBV is tightly latent within RS and RS cell variants of HIV-associated HD. It appears that factors other than host immune status are important in maintaining EBV latency in HIV-associated HD.
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PMID:Human immunodeficiency virus-associated Hodgkin's disease contains latent, not replicative, Epstein-Barr virus. 881 1

The type I membrane protein calnexin functions as a molecular chaperone for secretory glycoproteins in the endoplasmic reticulum with ATP and Ca2+ as two of the cofactors involved in substrate binding. Protease protection experiments with intact canine rough microsomes showed that amino acid residues 1-462 of calnexin are located within the lumen of the endoplasmic reticulum. Expression using the baculovirus Sf9 insect cell system of a recombinant truncated calnexin corresponding to residues 1-462 (calnexin delta TMC) revealed an association in vivo with a coexpressed secretory glycoprotein substrate, human immunodeficiency virus type I gp120. For the in vitro characterization of calnexin delta TMC, we purified this secreted form to homogeneity from the medium of Sf9 cells. We demonstrate that the properties of the purified calnexin delta TMC correspond to those of full-length calnexin in canine microsomes with at least one intramolecular disulfide bond and binding to 45Ca2+. Calnexin delta TMC underwent a marked and reversible conformational change following Ca2+ binding as measured by its resistance to proteinase K digestion of a 60-kDa fragment and also by the change from an oligomeric form of calnexin delta TMC to a monomeric form. We also found that calnexin bound Mg-ATP leading to a conformational change from a monomeric to an oligomeric form that coincided as with markedly increased proteinase sensitivity. Our results identify the luminal domain of calnexin as responsible for binding substrates, Ca2+, and Mg-ATP. Because Ca2+ and ATP are required in vivo for the maintenance of calnexin-substrate interactions, conformational changes in the luminal domain of calnexin induced by Ca2+ and Mg-ATP are relevant to the in vivo function of calnexin as a molecular chaperone.
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PMID:Conformational changes induced in the endoplasmic reticulum luminal domain of calnexin by Mg-ATP and Ca2+. 762 14

Human immunodeficiency virus-associated oral hairy leukoplakia (HLP) is characterized by coinfection with multiple types and strains of Epstein-Barr virus (EBV) and recombination within the EBV genome. HIV-seronegative immunosuppressed and immunocompetent patients with HLP were examined to determine the pathogenic contribution of EBV coinfection and recombination to the development of HLP. Multiple coinfecting EBV strains were detected in both HLP specimens and peripheral blood lymphocytes (PBL) of HIV-seronegative persons with HLP. One specific EBV strain was detected in HLP specimens from 3 of 4 patients. Also, viral recombination during productive replication within HLP generated variants of the latent membrane protein-1 (LMP-1) and nuclear antigen-2 (EBNA-2) genes. Some variants were also detected within PBL. Thus, EBV coinfection and recombination are consistent findings in persons with HLP regardless of immune status. Virally mediated determinants may be important features of EBV pathogenesis.
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PMID:Epstein-Barr virus coinfection and recombination in non-human immunodeficiency virus-associated oral hairy leukoplakia. 775 10

We describe two siblings with X-linked hyper-IgM immunodeficiency. One patient developed disseminated cryptococcosis. Co-culture of this patient's T cells with normal B cells suppressed IgG and IgA production. The CD40 ligand gene of one patient was examined and contained a nonsense mutation at nucleotide 475. CD40 ligand is a membrane protein which is expressed on activated T cells and induces B-cell proliferation. These results suggest that there is a defect in T- and B-cell interactions in this immunodeficiency syndrome. It is also possible that patients with this syndrome are predisposed to cryptococcal infections.
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PMID:Hyper-IgM immunodeficiency with disseminated cryptococcosis. 794 15

The small membrane protein Vpu of human immunodeficiency virus type 1 stimulates rapid degradation of CD4 molecules that are retained in the endoplasmic reticulum. To analyze the domain(s) of CD4 involved in Vpu-stimulated degradation, we examined degradation of hybrid proteins made between the vesicular stomatitis virus glycoprotein (VSV G) and CD4. Vpu expression stimulated rapid degradation of a hybrid consisting of the extracellular domain of VSV G linked to the transmembrane and cytoplasmic domains of CD4. Analysis of additional hybrids showed that both the cytoplasmic and transmembrane domains of CD4 were required for this Vpu-stimulated degradation. This conclusion is in apparent conflict with a recent study showing that the cytoplasmic domain of CD4 alone is sufficient to cause Vpu-stimulated degradation of a CD8-CD4 hybrid protein. The apparent conflict may be explained by the presence of related sequences or structures in the transmembrane domains of CD4 and CD8 that are involved in binding Vpu directly or that interact with the Vpu-stimulated degradation system.
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PMID:Stimulation of heterologous protein degradation by the Vpu protein of HIV-1 requires the transmembrane and cytoplasmic domains of CD4. 809 84

Epstein-Barr virus (EBV) DNA was detected in immunoblastic lymphoma arising in a child with the primary immunodeficiency, Wiskott-Aldrich syndrome. Southern blot analysis of the structure of the EBV genome revealed that the lymphoma was monoclonal and contained episomal EBV DNA. The EBV latent genes, latent membrane protein 1 (LMP1) and the EBV nuclear antigen 2 (EBNA2), were detected by immunohistochemistry in the Wiskott-Aldrich lymphoma but not in an EBV-positive Burkitt's lymphoma, implying that host immune factors could influence EBV gene expression. Hybridization in situ demonstrated expression of EBV-encoded RNA (EBER), the cellular c-fgr protooncogene, and CD23 B-cell activation transcripts in the Wiskott-Aldrich lymphoma whereas EBER and c-fgr but not CD23 were expressed in the Burkitt's lymphoma. These data suggest that in primary immunodeficiency-related lymphoma, LMP1 and EBNA2 are expressed and that this expression correlates with expression of CD23. This supports previous in vitro studies showing that CD23 is specifically induced by LMP1 or EBNA2 genes. In contrast, expression of c-fgr may be independent of expression of these EBV latent genes.
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PMID:Epstein-Barr virus-related lymphomagenesis in a child with Wiskott-Aldrich syndrome. 811 28


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