Soluble Epstein-Barr Virus Glycoproteins gH, gL, and gp42 Form a 1:1:1 Stable Complex That Acts Like Soluble gp42 in B-Cell Fusion but Not in Epithelial Cell Fusion

Kirschner, Austin N.; Omerović, Jasmina; Попов, Б. В.; Longnecker, Richard; Jardetzky, Theodore S.

doi:10.1128/jvi.00572-06

Cited by 75 publications

(118 citation statements)

References 36 publications

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“…This putative site for gp42 binding is near to the integrin binding loop, and competitive binding between gp42 and integrin to gH/gL would be consistent with the observation that gp42 and gp42-derived peptides block fusion with epithelial cells (9,13,14,16).…”

Section: Resultsmentioning

confidence: 52%

“…The ectodomains of EBV gH and gL were coexpressed in insect cells. The two proteins form a stable complex and were purified by affinity chromatography with an antibody (E1D1) that recognizes an epitope dependent on both gH and gL (13,29). The complex elutes in gel filtration chromatography with the expected molecular weight of the heterodimer (13).…”

Section: Resultsmentioning

confidence: 99%

“…The expression and purification of soluble EBV gH/gL has been previously described (13). In the expression constructs, gH residues 18-679 and gL residues 24-137 were fused to the baculovirus gp64 signal sequence, resulting in the addition of three N-terminal residues (AMT) into gH and three (AMD) into gL.…”

Section: Methodsmentioning

confidence: 99%

“…gp42 has multiple functional sites for interaction with gH/gL, HLA class II, and potentially, another unknown binding ligand that could be engaged through a large surface-exposed hydrophobic pocket (6)(7)(8)(9)(10)(11)(12). The gp42 protein binds to the gH/gL complex with nanomolar affinity through its N-terminal region, and this interaction can be recapitulated with a synthetic peptide of ∼35 aa residues (10,13,14). EBV glycoprotein-mediated membrane fusion with epithelial cells does not require gp42 but only gB and gH/gL, and fusion can be completely blocked by saturating amounts of either gp42 or short gp42-derived peptides (13)(14)(15)(16), consistent with the hypothesis that gp42 levels in the virion regulate the cellular tropism of the virus in vivo (16).…”

mentioning

confidence: 99%

“…The gp42 protein binds to the gH/gL complex with nanomolar affinity through its N-terminal region, and this interaction can be recapitulated with a synthetic peptide of ∼35 aa residues (10,13,14). EBV glycoprotein-mediated membrane fusion with epithelial cells does not require gp42 but only gB and gH/gL, and fusion can be completely blocked by saturating amounts of either gp42 or short gp42-derived peptides (13)(14)(15)(16), consistent with the hypothesis that gp42 levels in the virion regulate the cellular tropism of the virus in vivo (16). Recent observations indicate that EBV gH/gL engages integrins αvβ6 and/or αvβ8 on epithelial cells to trigger membrane fusion and entry (17).…”

mentioning

confidence: 99%

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Crystal structure of the Epstein-Barr virus (EBV) glycoprotein H/glycoprotein L (gH/gL) complex

Matsuura

Kirschner

Longnecker

et al. 2010

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

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The Epstein-Barr virus (EBV) is a γ-herpesvirus that infects B cells and epithelial cells and that has been linked to malignancies in both cell types in vivo. EBV, like other herpesviruses, has three glycoproteins, glycoprotein B (gB), gH, and gL, that form the core membrane fusion machinery mediating viral penetration into the cell. The gH and gL proteins associate to form a heterodimeric complex, which is necessary for efficient membrane fusion and also implicated in direct binding to epithelial cell receptors required for viral entry. To gain insight into the mechanistic role of gH/gL, we determined the crystal structure of the EBV gH/gL complex. The structure is comprised of four domains organized along the longest axis of the molecule. Comparisons with homologous HSV-2 gH/gL and partial pseudorabies virus gH structures support the domain boundaries determined for the EBV gH/gL structure and illustrate significant differences in interdomain packing angles. The gL subunit and N-terminal residues of gH form a globular domain at one end of the structure, implicated in interactions with gB and activation of membrane fusion. The C-terminal domain of gH, proximal to the viral membrane, is also implicated in membrane fusion. The gH/gL structure locates an integrin binding motif, implicated in epithelial cell entry, on a prominent loop in the central region of the structure. Multiple regions of gH/gL, including its two extreme ends, are functionally important, consistent with the multiple roles of gH/gL in EBV entry.

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Section: Resultsmentioning

confidence: 52%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Crystal structure of the Epstein-Barr virus (EBV) glycoprotein H/glycoprotein L (gH/gL) complex

Matsuura

Kirschner

Longnecker

et al. 2010

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

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151

205

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Anti‐EBV antibodies: Roles in diagnosis, pathogenesis, and antiviral therapy

Xie

Zhong

et al. 2023

Journal of Medical Virology

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Epstein-Barr virus (EBV) infection is prevalent in global population and associated with multiple malignancies and autoimmune diseases. During the infection, EBV-harbored or infected cell-expressing antigen could elicit a variety of antibodies with significant role in viral host response and pathogenesis. These antibodies have been extensively evaluated and found to be valuable in predicting disease diagnosis and prognosis, exploring disease mechanisms, and developing antiviral agents. In this review, we discuss the versatile roles of EBV antibodies as important biomarkers for EBV-related diseases, potential driving factors of autoimmunity, and promising therapeutic agents for viral infection and pathogenesis.

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Epstein–Barr Virus Entry

Longnecker¹,

Hutt-Fletcher²,

Jardetzky³

2008

DNA Tumor Viruses

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Entry of Epstein-Barr virus into human lymphoblastoid cells (Daudi cells) was studied by electron microscopy. At the site of viral attachment, two distinct interactions conducive to penetration of the virus occurred between the viral envelope and cell membrane, namely, (i) simultaneous dissolution of both the envelope and cell membrane, presumably resulting in passage of viral capsids into the cytoplasm and (ii) dissolution confined to the cell membrane with resulting penetration of enveloped virus. In the latter case envelope dissolution appears to occur subsequently in the cytoplasm with release of capsids. Fusion of the viral envelope with the cell membrane was not observed. The capsids exhibited two distinct structural forms one dense, the other translucent or light in appearance. The former disrupted near the cell membrane with release of viral cores into the cytoplasm whereas the light capsids containing dense cores migrated toward the nucleus and accumulated in the perinuclear region. Apparently the process of releasing deoxyribonucleic acid (DNA) from the light capsid is slowed down or prevented in Daudi cells. A hypothesis is presented concerning the manner in which these two types of capsids initiate infection.

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Soluble Epstein-Barr Virus Glycoproteins gH, gL, and gp42 Form a 1:1:1 Stable Complex That Acts Like Soluble gp42 in B-Cell Fusion but Not in Epithelial Cell Fusion

Cited by 75 publications

References 36 publications

Crystal structure of the Epstein-Barr virus (EBV) glycoprotein H/glycoprotein L (gH/gL) complex

Crystal structure of the Epstein-Barr virus (EBV) glycoprotein H/glycoprotein L (gH/gL) complex

Anti‐EBV antibodies: Roles in diagnosis, pathogenesis, and antiviral therapy

Epstein–Barr Virus Entry

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