Infectious Epstein-Barr Virus Lacking Major Glycoprotein BLLF1 (gp350/220) Demonstrates the Existence of Additional Viral Ligands

Janz, Annette; Oezel, Muhsin; Kurzeder, Christian; Mautner, Josef; Pich, Dagmar; Kost, Manuela; Hammerschmidt, Wolfgang; Delecluse, Henri Jacques

doi:10.1128/jvi.74.21.10142-10152.2000

Cited by 147 publications

(144 citation statements)

References 50 publications

Supporting

Mentioning

137

Contrasting

Unclassified

Order By: Relevance

“…For B cells, gp350 is not required for EBVinduced cell fusion, but gp42, gB, gH, and gL are necessary and sufficient (8). gp350 is dispensable for entry given that a virus lacking gp350 still infects numerous lymphoid and epithelial cell lines (43). To examine the requirements for epithelial cell fusion, CHO-K1 cells were transfected with different combinations of viral glycoproteins along with a plasmid containing the T7 promoter upstream of a luciferase reporter.…”

Section: Results Gb Gh and Gl Mediate Efficient Fusion With Some Humentioning

confidence: 99%

Cell-surface expression of a mutated Epstein–Barr virus glycoprotein B allows fusion independent of other viral proteins

McShane

Longnecker

2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Epstein-Barr virus (EBV) infects human B lymphocytes and epithelial cells. We have compared the requirements for EBV glycoprotein-induced cell fusion between Chinese hamster ovary effecter cells and human B lymphoblasts or epithelial cells by using a virus-free cell fusion assay. EBV-encoded gB, gH, gL, and gp42 glycoproteins were required for efficient B cell fusion, whereas EBV gB, gH, and gL glycoproteins were required for Chinese hamster ovary effecter cell fusion with epithelial cell lines (AGS and SCC68) or the human embryonic kidney cell line 293-P. Fusion with human embryonic kidney 293-P cells was greater than fusion observed with B cells, indicative of an important role for cell contact. An antibody directed against the gH and gL complex inhibited epithelial cell fusion. Increased surface expression of gB alone as a result of truncations or point mutants in the carboxyl-terminal tail allowed gB-mediated fusion with epithelial cells, albeit at a lower level than with coexpression of gB, gH, and gL. Overall, gB appears to be the critical component for EBV glycoprotein-mediated cell fusion. viral entry ͉ herpesvirus T he entry process of human herpesviruses entails a two-step process: binding followed by fusion. Specific herpesvirusencoded glycoproteins and cell-surface receptors are important for both events (1-3). Entry may occur by free virus infecting a cell or by cell-cell spread (2). In either case, fusion is a prerequisite for infection. Despite herpesvirus genomes encoding many viral glycoproteins, the glycoproteins implicated in entry and fusion are limited and conserved (1). Most herpesviruses require the conserved glycoproteins gH, gL, and gB, as well as an additional, family-specific viral glycoprotein, such as gD for ␣-herpesviruses or gp42 for the ␥-herpesvirus Epstein-Barr virus (EBV), for efficient entry and fusion (1). These nonconserved glycoproteins result in cell specificity by recognizing distinct cellular receptors. For example, EBV glycoprotein 42 binds to HLA class II on B cells, an interaction essential for the infection of B cells (4, 5). Additionally, EBV gp350͞220 binds to the B cell-surface receptor CD21͞CR2, and this binding mediates the initial interaction of EBV with B cells and is thought to tether the virus to promote the subsequent binding of gp42 to HLA class II (6, 7). The gp42-class II interaction is then proposed to trigger membrane fusion, a reaction mediated by gH (EBV gp85), gL (EBV gp25), and gB (EBV gp110) (8). The exact role each of these glycoproteins plays in fusion is unclear.EBV can enter cells by means of two routes, depending on the host cell type. In primary human lymphocytes, EBV is endocytosed before fusion, whereas, in B cells in culture, the virion envelope directly fuses with the plasma membrane (9, 10). Similarly to B cells in culture, fusion of EBV with epithelial cells occurs by direct fusion of the virion envelope with the plasma membrane. Despite B lymphocytes being the primary site for latency, the tropism of EBV for epithelial cells is suppor...

show abstract

Section: Results Gb Gh and Gl Mediate Efficient Fusion With Some Humentioning

confidence: 99%

Cell-surface expression of a mutated Epstein–Barr virus glycoprotein B allows fusion independent of other viral proteins

McShane

Longnecker

2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The relative increase in the number of encapsidated KSHV virions after transient expression of K8.1 suggests that K8.1 may facilitate virion morphogenesis. A similar scenario may occur for EBV gp350/220, since deletion of the gp350/220 gene caused a decrease in infectivity which was complemented in trans by exogenously supplied gp350/220 (24).…”

mentioning

confidence: 79%

“…The K8.1 gene has attracted significant interest due to the fact that it is positionally colinear to the EBV major glycoprotein gp350/220 gene (20), the murine gammaherpesvirus 68 gp150 gene (53), the herpesvirus saimiri ORF51 gene (5), and the bovine herpesvirus 4 BOEFD1 gene (36,48). EBV gp350/ 220 has been shown to be involved in the binding of the virus to target cells by means of the CD21 receptor on B cells (15,(38)(39)(40)55); however, gp350/220 is not required for virus entry into fibroblasts (24).…”

mentioning

confidence: 99%

Kaposi's Sarcoma-Associated Herpesvirus Glycoprotein K8.1 Is Dispensable for Virus Entry

Luna

Zhou

Baghian³

et al. 2004

J Virol

View full text Add to dashboard Cite

show abstract

“…Although dispensable for infectivity, gp350 is important for the initial attachment to B cells (80) and has been shown to be highly O-glycosylated (81). gp350 also represents a very potent immunogen (82,83). On gp350, 19 O-glycosites were identified, 18 of which were located in the Pro/Ser/Thr-rich mucin-like stem region, and 1 glycosite was found at the tip of one of the N-terminal domains (Fig.…”

Section: Mapping O-glycosites In Human Herpesvirusesmentioning

confidence: 99%

Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus

Bagdonaite

Nordén

Joshi

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Herpesviruses are among the most complex and widespread viruses, infection and propagation of which depend on envelope proteins. These proteins serve as mediators of cell entry as well as modulators of the immune response and are attractive vaccine targets. Although envelope proteins are known to carry glycans, little is known about the distribution, nature, and functions of these modifications. This is particularly true for O-glycans; thus we have recently developed a "bottom up" mass spectrometry-based technique for mapping O-glycosylation sites on herpes simplex virus type 1. We found wide distribution of O-glycans on herpes simplex virus type 1 glycoproteins and demonstrated that elongated O-glycans were essential for the propagation of the virus. Here, we applied our proteome-wide discovery platform for mapping O-glycosites on representative and clinically significant members of the herpesvirus family: varicella zoster virus, human cytomegalovirus, and Epstein-Barr virus. We identified a large number of O-glycosites distributed on most envelope proteins in all viruses and further demonstrated conserved patterns of O-glycans on distinct homologous proteins. Because glycosylation is highly dependent on the host cell, we tested varicella zoster virus-infected cell lysates and clinically isolated virus and found evidence of consistent O-glycosites. These results present a comprehensive view of herpesvirus O-glycosylation and point to the widespread occurrence of O-glycans in regions of envelope proteins important for virus entry, formation, and recognition by the host immune system. This knowledge enables dissection of specific functional roles of individual glycosites and, moreover, provides a framework for design of glycoprotein vaccines with representative glycosylation.

show abstract

Infectious Epstein-Barr Virus Lacking Major Glycoprotein BLLF1 (gp350/220) Demonstrates the Existence of Additional Viral Ligands

Cited by 147 publications

References 50 publications

Cell-surface expression of a mutated Epstein–Barr virus glycoprotein B allows fusion independent of other viral proteins

Cell-surface expression of a mutated Epstein–Barr virus glycoprotein B allows fusion independent of other viral proteins

Kaposi's Sarcoma-Associated Herpesvirus Glycoprotein K8.1 Is Dispensable for Virus Entry

Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus

Contact Info

Product

Resources

About