scholarly journals CD23 (Fc∊RII) release from cell membranes is mediated by a membrane-bound metalloprotease

1998 ◽  
Vol 333 (3) ◽  
pp. 573-579 ◽  
Author(s):  
Ariane E. MAROLEWSKI ◽  
Derek R. BUCKLE ◽  
Gary CHRISTIE ◽  
David L. EARNSHAW ◽  
Pearl L. FLAMBERG ◽  
...  
Keyword(s):  
Cell Surface ◽  
Serine Proteases ◽  
Plasma Membranes ◽  
Gel Filtration ◽  
Cell Types ◽  
Cysteine Proteases ◽  
Integral Membrane Protein ◽  
Monocytic Cell ◽  
Barr Virus ◽  
Epstein Barr

CD23 (low-affinity IgE receptor, FcεRII) is expressed as a Type II extracellular protein on a variety of cells such as B-cells, monocytes and macrophages and is cleaved from the cell surface to generate several distinct fragments. The expression of CD23 on the cell surface as well as the generation of soluble fragments of CD23 has been shown to be involved in the regulation of IgE synthesis. Here we report that the release of CD23 from the cell surface is mediated by a metalloprotease. An assay utilizing purified CD23 and an neo-epitope antibody specific for one of the known cleavage products is described and used to demonstrate unambiguously the cleavage of CD23 by a distinct protease. Characterization of the mechanism of CD23 processing shows that the protease exists as an integral membrane protein with a functional molecular mass of approx. 63 kDa as determined by gel-filtration chromatography. The CD23-cleaving activity found in enriched plasma membranes from RPMI 8866 cells is inhibited by the metalloprotease inhibitors 1,10-phenanthroline and imidazole and by the matrix metalloprotease inhibitor batimastat, but not by inhibitors of cysteine proteases, serine proteases or acid proteases. The same or a similar activity that cleaves CD23 to the known 33 kDa fragment and is inhibited by batimastat is present in diverse cell types such as unstimulated fibroblasts and monocytic cell lines not expressing CD23, as well as in the Epstein–Barr virus-transformed B-cell line, RPMI 8866, which constitutively expresses CD23.

Cell surface alteration in Epstein-Barr virus-transformed cells from patients with extreme insulin resistance

Diabetes ◽  
1990 ◽  
Vol 39 (8) ◽  
pp. 924-927 ◽  
Author(s):  
D. L. Gorden ◽  
A. Robert ◽  
V. Y. Moncada ◽  
S. I. Taylor ◽  
J. Muhlhauser ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cell Surface ◽  
Epstein Barr Virus ◽  
Transformed Cells ◽  
Barr Virus ◽  
Surface Alteration ◽  
Extreme Insulin Resistance ◽  
Epstein Barr

scholarly journals Absence of allogeneic restriction in human T-cell-mediated cytotoxicity to Epstein-Barr virus-infected target cells. Demonstration of an HLA-linked control at the effector level.

1979 ◽  
Vol 150 (6) ◽  
pp. 1310-1322 ◽  
Author(s):  
M Lipinski ◽  
W H Fridman ◽  
T Tursz ◽  
C Vincent ◽  
D Pious ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
Cell Surface ◽  
Target Cell ◽  
Epstein Barr Virus ◽  
Target Cells ◽  
Specific Lysis ◽  
Barr Virus ◽  
Positive Target ◽  
Epstein Barr

Peripheral T lymphocytes from patients with infectious mononucleosis (IM) are sensitized in vivo against the Epstein-Barr virus (EBV). The expression of HLA-A, B, or C molecules at the target cell surface is necessary for the cytotoxic reaction because (a) EBV-positive Daudi cells lacking HLA-A, B, and C determinants are resistant to anti-EBV T-cell lysis, (b) cytolysis of EBV-positive target cells can be consistently inhibited by anti-HLA-A, B, and C and anti-beta 2 microglobulin antibodies. However, no evidence for allogeneic restriction in this system was apparent as (a) cytotoxic T lymphocytes (CTL) from one given individual could exert a cytotoxicity of a similar magnitude on different EBV-positive target cells, regardless of the number of HLA-A or B specificities shared by the effectors and targets; (b) CTL from IM patients were able to kill target cells without any HLA-A or B antigen in common; and (c) T5-1 variants lacking one or two HLA antigens at the A, B, or D locus are killed to the same extent as the parental cells. 7 of the 9 IM patients with detectable circulating anti-EBV CTL carried the HLA-A1 antigen, whereas none of the 16 IM patients lacking detectable peripheral CTL were HLA-A1 positive (mean specific lysis of T5-1 target cells by T cells from HLA-A1 positive patients: 29.3 vs. 0.6% in HLA-A1-negative patients) (P less than 10(-9)). These data suggest an HLA-A1-linked gene control of the magnitude of the anti-EBV CTL response. Thus, the HLA region appears to act at two different level sin the T-cell-mediated lysis of EBV-infected cells by controlling first, the development of anti-EBV and second, the expression of HLA-A, B, and C molecules involved as recognition structures at the target cell surface.

scholarly journals Cell Surface Expression of Endosomal Toll-Like Receptors—A Necessity or a Superfluous Duplication?

2021 ◽  
Vol 11 ◽  
Author(s):  
Matylda Barbara Mielcarska ◽  
Magdalena Bossowska-Nowicka ◽  
Felix Ngosa Toka
Keyword(s):  
Immune Response ◽  
Cell Membrane ◽  
Cell Surface ◽  
Signaling Pathways ◽  
Distinct Group ◽  
Cell Types ◽  
Cysteine Proteases ◽  
Cell Surface Expression ◽  
Critical Event ◽  
Toll Like Receptors

Timely and precise delivery of the endosomal Toll-like receptors (TLRs) to the ligand recognition site is a critical event in mounting an effective antimicrobial immune response, however, the same TLRs should maintain the delicate balance of avoiding recognition of self-nucleic acids. Such sensing is widely known to start from endosomal compartments, but recently enough evidence has accumulated supporting the idea that TLR-mediated signaling pathways originating in the cell membrane may be engaged in various cells due to differential expression and distribution of the endosomal TLRs. Therefore, the presence of endosomal TLRs on the cell surface could benefit the host responses in certain cell types and/or organs. Although not fully understood why, TLR3, TLR7, and TLR9 may occur both in the cell membrane and intracellularly, and it seems that activation of the immune response can be initiated concurrently from these two sites in the cell. Furthermore, various forms of endosomal TLRs may be transported to the cell membrane, indicating that this may be a normal process orchestrated by cysteine proteases—cathepsins. Among the endosomal TLRs, TLR3 belongs to the evolutionary distinct group and engages a different protein adapter in the signaling cascade. The differently glycosylated forms of TLR3 are transported by UNC93B1 to the cell membrane, unlike TLR7, TLR8, and TLR9. The aim of this review is to reconcile various views on the cell surface positioning of endosomal TLRs and add perspective to the implication of such receptor localization on their function, with special attention to TLR3. Cell membrane-localized TLR3, TLR7, and TLR9 may contribute to endosomal TLR-mediated inflammatory signaling pathways. Dissecting this signaling axis may serve to better understand mechanisms influencing endosomal TLR-mediated inflammation, thus determine whether it is a necessity for immune response or simply a circumstantial superfluous duplication, with other consequences on immune response.

scholarly journals Comparative Mutagenesis of Pseudorabies Virus and Epstein-Barr Virus gH Identifies a Structural Determinant within Domain III of gH Required for Surface Expression and Entry Function

2015 ◽  
Vol 90 (5) ◽  
pp. 2285-2293 ◽  
Author(s):  
Britta S. Möhl ◽  
Christina Schröter ◽  
Barbara G. Klupp ◽  
Walter Fuchs ◽  
Thomas C. Mettenleiter ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cell Surface ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Pseudorabies Virus ◽  
Surface Expression ◽  
Structural Motif ◽  
Cell Surface Expression ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACTHerpesviruses infect cells using the conserved core fusion machinery composed of glycoprotein B (gB) and gH/gL. The gH/gL complex plays an essential but still poorly characterized role in membrane fusion and cell tropism. Our previous studies demonstrated that the conserved disulfide bond (DB) C278/C335 in domain II (D-II) of Epstein-Barr virus (EBV) gH has an epithelial cell-specific function, whereas the interface of D-II/D-III is involved in formation of the B cell entry complex by binding to gp42. To extend these studies, we compared gH of the alphaherpesvirus pseudorabies virus (PrV) with gH of the gammaherpesvirus EBV to identify functionally equivalent regions critical for gH function during entry. We identified several conserved amino acids surrounding the conserved DB that connects three central helices of D-III of PrV and EBV gH. The present study verified that the conserved DB and several contacting amino acids in D-III modulate cell surface expression and thereby contribute to gH function. In line with this finding, we found that DB C404/C439 and T401 are important for cell-to-cell spread and efficient entry of PrV. This parallel comparison between PrV and EBV gH function brings new insights into how gH structure impacts fusion function during herpesvirus entry.IMPORTANCEThe alphaherpesvirus PrV is known for its neuroinvasion, whereas the gammaherpesvirus EBV is associated with cancer of epithelial and B cell origin. Despite low amino acid conservation, PrV gH and EBV gH show strikingly similar structures. Interestingly, both PrV gH and EBV gH contain a structural motif composed of a DB and supporting amino acids which is highly conserved within theHerpesviridae. Our study verified that PrV gH uses a minimal motif with the DB as the core, whereas the DB of EBV gH forms extensive connections through hydrogen bonds to surrounding amino acids, ensuring the cell surface expression of gH/gL. Our study verifies that the comparative analysis of distantly related herpesviruses, such as PrV and EBV, allows the identification of common gH functions. In addition, we provide an understanding of how functional domains can evolve over time, resulting in subtle differences in domain structure and function.

Cell Surface Alteration in Epstein-Barr Virus-Transformed Cells From Patients With Extreme Insulin Resistance

Diabetes ◽  
1990 ◽  
Vol 39 (8) ◽  
pp. 924-927 ◽  
Author(s):  
D. L. Gorden ◽  
A. Robert ◽  
V. Y. Moncada ◽  
S. I. Taylor ◽  
J. Muhlhauser ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cell Surface ◽  
Epstein Barr Virus ◽  
Transformed Cells ◽  
Barr Virus ◽  
Surface Alteration ◽  
Extreme Insulin Resistance ◽  
Epstein Barr

Polylactosaminoglycan modification of a small integral membrane glycoprotein, influenza B virus NB

1988 ◽  
Vol 8 (3) ◽  
pp. 1186-1196
Author(s):  
M A Williams ◽  
R A Lamb
Keyword(s):  
Molecular Weight ◽  
Cell Surface ◽  
Gel Filtration ◽  
Cell Types ◽  
Influenza B Virus ◽  
Influenza B ◽  
Membrane Glycoprotein ◽  
Intact Cells ◽  
B Virus ◽  
Carbohydrate Chains

The structure of the carbohydrate components of NB, the small integral membrane glycoprotein of influenza B virus, was investigated. The carbohydrate chains of NB are processed from the high-mannose form (NB18) to a heterogeneous form of much higher molecular weight, designated NBp. Selection of this carbohydrate-containing form of NB with Datura stramonium lectin, its susceptibility to digestion by endo-beta-galactosidase, and determination of the size of NBp glycopeptides by gel filtration chromatography suggested that the increase in molecular weight is due to processing to polylactosaminoglycan. Investigation of the polypeptides produced by influenza B/Lee/40 virus infection of several cell types and another strain of influenza B virus suggested that the signal for modification to polylactosaminoglycan is contained in NB. Expression of mutants of NB lacking either one or both of the normal N-terminal sites of asparagine-linked glycosylation indicated that both carbohydrate chains are modified to contain polylactosaminoglycan. NBp and a small amount of unprocessed NB18 are expressed at the infected-cell surface, as determined by digestion of the surfaces of intact cells with various endoglycosidases. Unglycosylated NB, expressed either in influenza B virus-infected cells treated with tunicamycin or in cells expressing the NB mutant lacking both N-linked glycosylation sites, was expressed at the cell surface, indicating that NB does not require carbohydrate addition for transport.

scholarly journals Determination of Epstein-Barr Virus–Infected Lymphocyte Cell Types in Peripheral Blood Mononuclear Cells as a Valuable Diagnostic Tool in Hematological Diseases

2019 ◽  
Vol 6 (5) ◽  
Author(s):  
Peiling Zhang ◽  
Chen Zeng ◽  
Jiali Cheng ◽  
Jing Zhou ◽  
Jia Gu ◽  
...  
Keyword(s):  
Infected Cell ◽  
B Cell ◽  
Peripheral Blood Mononuclear Cells ◽  
Epstein Barr Virus ◽  
Nk Cell ◽  
Cell Types ◽  
Cell Type ◽  
Peripheral Blood Mononuclear ◽  
Barr Virus ◽  
Epstein Barr

Abstract Background High loads of Epstein-Barr virus (EBV) in peripheral blood mononuclear cells (PBMCs) can be indicative of a broad spectrum of diseases, ranging from asymptomatic infection to fatal cancers. Methods We retrospectively investigated the EBV-infected cell types in PBMCs among 291 patients. Based on EBV-infected cell types, the clinical features and prognoses of 93 patients with EBV-associated (EBV+) T/natural killer (NK)–cell lymphoproliferative diseases (LPDs) T/NK-LPDs) were investigated over a 5-year period. Results Although B-cell-type infection was found in immunocompromised patients and patients with asymptomatic high EBV carriage, infectious mononucleosis, EBV+ B-cell LPDs and B-cell lymphomas, T-cell, NK-cell or multiple-cell-type infection in immunocompetent hosts were highly suggestive of EBV+ T/NK-LPDs, EBV+ T/NK-cell lymphomas, and aggressive NK-cell leukemia. Patients with non–B-cell infection had a poorer prognosis than those with B-cell-type infection. In our cohort, 79.6% of patients with EBV+ T/NK-LPDs were >18 years old, and NK cells were identified as EBV-infected cell type in 54.8%. Nearly half of patients with EBV+ T/NK-LPDs had genetic defects associated with immunodeficiency. However, hemophagocytic lymphohistiocytosis, and not genetic defects, was the only parameter correlated with poor prognosis of EBV+ T/NK-LPDs. Conclusions Determination of EBV-infected cell types among PBMCs is a valuable tool for the differential diagnosis of EBV+ hematological diseases. In this study, determination of Epstein-Barr virus-infected cell types in peripheral blood mononuclear cells of 291 patients with high Epstein-Barr virus loads were retrospectively investigated, which indicate it is a valuable tool for Epstein-Barr virus-associated hematological diseases.

scholarly journals Low expression of lymphocyte function-associated antigen (LFA)-1 and LFA-3 adhesion molecules is a common trait in Burkitt's lymphoma associated with and not associated with Epstein-Barr virus

Blood ◽  
1990 ◽  
Vol 75 (9) ◽  
pp. 1827-1833 ◽  
Author(s):  
M Billaud ◽  
F Rousset ◽  
A Calender ◽  
M Cordier ◽  
JP Aubry ◽  
...  
Keyword(s):  
Cell Surface ◽  
B Cell ◽  
Adhesion Molecules ◽  
Epstein Barr Virus ◽  
Burkitt’S Lymphoma ◽  
Receptor Activation ◽  
Burkitt's Lymphoma ◽  
Lymphocyte Function ◽  
Barr Virus ◽  
Epstein Barr

Abstract Lymphocyte function-associated antigens 1 and 3 (LFA-1, LFA-3) and intercellular adhesion molecule 1 (ICAM-1) are cell surface adhesion molecules necessary for immune processes requiring intercellular contact. It was recently proposed that malignant Burkitt's lymphoma cells (BL) may escape from immunosurveillance through the downregulation of LFA-1 (CD11a/CD18) or LFA-3 (CD58) and ICAM-1 (CD54) molecules. Expression of these three adhesion antigens was investigated in 19 BL lines. LFA-1 or LFA-3 expression was found to be absent or low in 8 of 11 Epstein-Barr virus (EBV) genome positive BL, but strongly expressed on all nonmalignant EBV genome positive lymphoblastoid cell lines (LCL). Negative or weak expression of LFA-1 and LFA-3 was also observed in 7 of 8 EBV genome negative BL. ICAM-1 was found to be expressed on the cell surface of the majority of BL lines. BL lines growing as individual cells did not express LFA-1, whereas clump- forming BL lines expressed this marker involved in B-cell homotypic aggregation. Expression of LFA-1 and LFA-3 was induced on in vitro infection of EBV-negative BL cells with the immortalizing EBV strain B95–8, and weakly with the nonimmortalizing EBV strain P3HR1. EBNA2 and LMP, two EBV encoded proteins expressed in LCL and in BL infected with B95–8 (BL/B95–8), are not expressed in P3HR1 infected BL cells (BL/P3HR1). Stable expression of EBNA2 after gene transfer in a BL/P3HR1 cell line did not restore the level of LFA-1 and LFA-3 found on BL/B95–8 cells. In EBV-positive BL cells expressing LFA-1 and LFA-3, LMP was found coexpressed, supporting the recent finding of the role of LMP in B-cell adhesion receptor activation. Consequently, diminished LFA-1 and LFA-3 expression appears to be a common characteristic of numerous EBV-positive BL as well as EBV-negative BL. These findings are discussed in the framework of BL pathogenesis.

scholarly journals The BRRF1 Early Gene of Epstein-Barr Virus Encodes a Transcription Factor That Enhances Induction of Lytic Infection by BRLF1

2004 ◽  
Vol 78 (10) ◽  
pp. 4983-4992 ◽  
Author(s):  
Gregory K. Hong ◽  
Henri-Jacques Delecluse ◽  
Henri Gruffat ◽  
Thomas E. Morrison ◽  
Wen-Hai Feng ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Epstein Barr Virus ◽  
Cell Types ◽  
Early Gene ◽  
Barr Virus ◽  
Ebv Infection ◽  
Early Protein ◽  
293 Cells ◽  
Latently Infected ◽  
Epstein Barr

ABSTRACT The switch from the latent to the lytic form of Epstein-Barr virus (EBV) infection is mediated by expression of the viral immediate-early (IE) proteins, BZLF1 (Z) and BRLF1 (R). An EBV early protein, BRRF1 (Na), is encoded by the opposite strand of the BRLF1 intron, but the function of this nuclear protein in the viral life cycle is unknown. Here we demonstrate that Na enhances the R-mediated induction of lytic EBV infection in 293 cells latently infected with a recombinant EBV (R-KO) defective for the expression of both R and Na. Na also enhances R-induced lytic infections in a gastric carcinoma line (AGS) carrying the R-KO virus, although it has no effect in a Burkitt lymphoma line (BL-30) stably infected with the same mutant virus. We show that Na is a transcription factor that increases the ability of R to activate Z expression from the R-KO viral genome in 293 cells and that Na by itself activates the Z promoter (Zp) in EBV-negative cells. Na activation of Zp requires a CRE motif (ZII), and a consensus CRE motif is sufficient to transfer Na responsiveness to the heterologous E1b promoter. Furthermore, we show that Na enhances the transactivator function of a Gal4-c-Jun fusion protein but does not increase the transactivator function of other transcription factors (including ATF-1, ATF-2, and CREB) known to bind CRE motifs. Na expression in cells results in increased levels of a hyperphosphorylated form of c-Jun, suggesting a mechanism by which Na activates c-Jun. Our results indicate that Na is a transcription factor that activates the EBV Zp IE promoter through its effects on c-Jun and suggest that Na cooperates with BRLF1 to induce the lytic form of EBV infection in certain cell types.

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