scholarly journals Functional Analysis of Glycoprotein L (gL) from Rhesus Lymphocryptovirus in Epstein-Barr Virus-Mediated Cell Fusion Indicates a Direct Role of gL in gB-Induced Membrane Fusion

2009 ◽  
Vol 83 (15) ◽  
pp. 7678-7689 ◽  
Author(s):  
Aileen E. Plate ◽  
Jasmina Smajlović ◽  
Theodore S. Jardetzky ◽  
Richard Longnecker
Keyword(s):  
Cell Surface ◽  
Cell Fusion ◽  
Epstein Barr Virus ◽  
Surface Expression ◽  
Host Cells ◽  
Cell Surface Expression ◽  
Direct Role ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACT Glycoprotein L (gL), which complexes with gH, is a conserved herpesvirus protein that is essential for Epstein-Barr virus (EBV) entry into host cells. The gH/gL complex has a conserved role in entry among herpesviruses, yet the mechanism is not clear. To gain a better understanding of the role of gL in EBV-mediated fusion, chimeric proteins were made using rhesus lymphocryptovirus (Rh-LCV) gL (Rh gL), which shares a high sequence homology with EBV gL but does not complement EBV gL in mediating fusion with B cells. A reduction in fusion activity was observed with chimeric gL proteins that contained the amino terminus of Rh gL, although they retained their ability to process and transport gH/gL to the cell surface. Amino acids not conserved within this region in EBV gL when compared to Rh gL were further analyzed, with the results mapping residues 54 and 94 as being functionally important for EBV-mediated fusion. All chimeras and mutants displayed levels of cell surface expression similar to that of wild-type gL and interacted with gH and gp42. Our data also suggest that the role of gL involves the activation or recruitment of gB with the gH/gL complex, as we found that reduced fusion of Rh gL, EBV/Rh-LCV chimeras, and gL point mutants could be restored by replacing EBV gB with Rh gB. These observations demonstrate a distinction between the role of gL in the processing and trafficking of gH to the cell surface and a posttrafficking role in cell-cell fusion.

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.

scholarly journals Mapping the N-Terminal Residues of Epstein-Barr Virus gp42 That Bind gH/gL by Using Fluorescence Polarization and Cell-Based Fusion Assays

2010 ◽  
Vol 84 (19) ◽  
pp. 10375-10385 ◽  
Author(s):  
Fengling Liu ◽  
Gaby Marquardt ◽  
Austin N. Kirschner ◽  
Richard Longnecker ◽  
Theodore S. Jardetzky
Keyword(s):  
Epithelial Cell ◽  
Viral Infection ◽  
B Cell ◽  
Cell Fusion ◽  
Viral Entry ◽  
Fluorescence Polarization ◽  
Epstein Barr Virus ◽  
Host Cells ◽  
Barr Virus ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) requires at a minimum membrane-associated glycoproteins gB, gH, and gL for entry into host cells. B-cell entry additionally requires gp42, which binds to gH/gL and triggers viral entry into B cells. The presence of soluble gp42 inhibits membrane fusion with epithelial cells by forming a stable heterotrimer of gH/gL/gp42. The interaction of gp42 with gH/gL has been previously mapped to residues 36 to 81 at the N-terminal region of gp42. In this study, we further mapped this region to identify essential features for binding to gH/gL by use of synthetic peptides. Data from fluorescence polarization, cell-cell fusion, and viral infection assays demonstrated that 33 residues corresponding to 44 to 61 and 67 to 81 of gp42 were indispensable for maintaining low-nanomolar-concentration gH/gL binding affinity and inhibiting B-cell fusion and epithelial cell fusion as well as viral infection. Overall, specific, large hydrophobic side chain residues of gp42 appeared to provide critical interactions, determining the binding strength. Mutations of these residues also diminished the inhibition of B-cell and epithelial cell fusions as well as EBV infection. A linker region (residues 62 to 66) between two gH/gL binding regions served as an important spacer, but individual amino acids were not critical for gH/gL binding. Probing the binding site of gH/gL and gp42 with gp42 peptides is critical for a better understanding of the interaction of gH/gL with gp42 as well as for the design of novel entry inhibitors of EBV and related human herpesviruses.

Extramedullary Plasmacytoma in a Patient with Aids: Report of a Case and Review of the Literature

1998 ◽  
Vol 84 (4) ◽  
pp. 511-514 ◽  
Author(s):  
Daniele Vallisa ◽  
Leonardo Pagani ◽  
Raffaella Bertè ◽  
Giuseppe Civardi ◽  
Pierluigi Viale ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Extramedullary Plasmacytoma ◽  
Tumor Cell Growth ◽  
Review Of The Literature ◽  
Direct Role ◽  
Barr Virus ◽  
Ebv Infection ◽  
Immunodeficiency Virus ◽  
Epstein Barr

Human immunodeficiency virus (HIV) is likely to play a role in the onset of plasma cell tumors (PCT). In fact, HIV could be involved in plasmacytomagenesis in several ways: it has the ability to lessen the immunosurveillance to such a degree as to impair the immune response against tumor cell growth. This decreased immunosurveillance could further facilitate the transforming malignant role of possible Epstein-Barr virus (EBV) infection occurring in this setting. Lastly, a murine retrovirus has been shown to be able to accelerate plasmacytomagenesis in mice, thus indicating that these viruses may be directly involved in the onset of PCT. According to cases previously reported in the literature, the clinical features of this case of HIV-associated PCT were more aggressive and the survival was shorter than expected for PCT cases in the general population. Further, the pattern of alteration of gam-maglobulinemia differed in this setting. These alterations strongly suggest a direct role of HIV in PCT. Further in-depth investigations are therefore warranted to elucidate this issue.

scholarly journals The Lytic Cycle of Epstein-Barr Virus Is Associated with Decreased Expression of Cell Surface Major Histocompatibility Complex Class I and Class II Molecules

2002 ◽  
Vol 76 (16) ◽  
pp. 8179-8188 ◽  
Author(s):  
Sinéad Keating ◽  
Stuart Prince ◽  
Matthew Jones ◽  
Martin Rowe
Keyword(s):  
Cell Surface ◽  
Mhc Class I ◽  
Surface Expression ◽  
Lytic Cycle ◽  
Class I ◽  
Cell Surface Expression ◽  
Barr Virus ◽  
Histocompatibility Complex ◽  
Infected Cells ◽  
Epstein Barr

ABSTRACT Human herpesviruses utilize an impressive range of strategies to evade the immune system during their lytic replicative cycle, including reducing the expression of cell surface major histocompatibility complex (MHC) and immunostimulatory molecules required for recognition and lysis by virus-specific cytotoxic T cells. Study of possible immune evasion strategies by Epstein-Barr virus (EBV) in lytically infected cells has been hampered by the lack of an appropriate permissive culture model. Using two-color immunofluorescence staining of cell surface antigens and EBV-encoded lytic cycle antigens, we examined EBV-transformed B-cell lines in which a small subpopulation of cells had spontaneously entered the lytic cycle. Cells in the lytic cycle showed a four- to fivefold decrease in cell surface expression of MHC class I molecules relative to that in latently infected cells. Expression of MHC class II molecules, CD40, and CD54 was reduced by 40 to 50% on cells in the lytic cycle, while no decrease was observed in cell surface expression of CD19, CD80, and CD86. Downregulation of MHC class I expression was found to be an early-lytic-cycle event, since it was observed when progress through late lytic cycle was blocked by treatment with acyclovir. The immediate-early transactivator of the EBV lytic cycle, BZLF1, did not directly affect expression of MHC class I molecules. However, BZLF1 completely inhibited the upregulation of MHC class I expression mediated by the EBV cell-transforming protein, LMP1. This novel function of BZLF1 elucidates the paradox of how MHC class I expression can be downregulated when LMP1, which upregulates MHC class I expression in latent infection, remains expressed in the lytic cycle.

The role of Epstein–Barr virus-encoded latent membrane proteins in host immune escape

2021 ◽  
Author(s):  
Yuanyuan Jiang ◽  
Yuan Ding ◽  
Shuzhen Liu ◽  
Bing Luo
Keyword(s):  
Membrane Proteins ◽  
Epstein Barr Virus ◽  
Immune Escape ◽  
Immune Surveillance ◽  
Host Cells ◽  
Barr Virus ◽  
Type Iv ◽  
Infection Pattern ◽  
Epstein Barr

Epstein–Barr virus (EBV) is a type IV herpesvirus that widely infects the vast majority of adults, and establishes a latent infection pattern in host cells to escape the clearance of immune system. The virus is intimately associated with the occurrence and progression of lymphomas and epithelial cell cancers. EBV latent membrane proteins (LMPs) can assist its immune escape by downregulating host immune response. Besides EBV, LMPs have important effects on the functions of exosomes and autophagy, which also help EBV to escape immune surveillance. These escape mechanisms may provide conditions for further development of EBV-associated tumors. In this article, we discussed the potential functions of EBV-encoded LMPs in promoting immune escape.

scholarly journals Hydrophobic Residues That Form Putative Fusion Loops of Epstein-Barr Virus Glycoprotein B Are Critical for Fusion Activity

2007 ◽  
Vol 81 (17) ◽  
pp. 9596-9600 ◽  
Author(s):  
Marija Backovic ◽  
Theodore S. Jardetzky ◽  
Richard Longnecker
Keyword(s):  
Epstein Barr Virus ◽  
Surface Expression ◽  
Glycoprotein B ◽  
Cell Surface Expression ◽  
Hydrophobic Residues ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT To test the importance of the hydrophobic residues within the putative Epstein-Barr virus (EBV) glycoprotein B (gB) fusion loops in membrane fusion, WY112-113 and WLIW193-196 were mutated into alanine, glutamic acid, or the analogous residues from herpes simplex virus type 1 (HSV-1) gB (HR and RVEA). All gB variants exhibited cell surface expression, demonstrating that the substitutions did not perturb gB trafficking. None of six gB variants was, however, capable of mediating fusion with either epithelial or B cells. These data demonstrate that the bulky and hydrophobic EBV loop residues, which differ from the more hydrophilic HSV-1 residues and appear more compatible with membrane insertion, are essential for EBV gB-dependent fusion.

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
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