The evolution of Epstein-Barr virus inferred from the conservation and mutation of the virus glycoprotein gp350/220 gene

Kawaguchi, Asako; Kanai, Koomi; Satoh, Yukio; Touge, Chizu; Nagata, Kazuhiro; Sairenji, Takeshi; Inoue, Yoshitsugu

doi:10.1007/s11262-008-0323-0

Cited by 11 publications

(7 citation statements)

References 46 publications

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“…13 The amino portion of gp350, which includes the amino acids important for binding to CD21, is more highly conserved than the carboxyl portion of the glycoprotein. 14,15 A potent neutralizing antibody, 72A1 that recognizes gp350, neutralizes type 1 and 2 EBV strains. 16 Of all the EBV glycoproteins, gp350 is the principle target for antibodies that neutralize infection of B cells, [17][18][19] and the glycoprotein is a target for antibody-dependent cellular cytotoxicity, 20,21 CD4 T cells, 22,23 and CD8 T cells.…”

Section: Ebv Glycoproteinsmentioning

confidence: 99%

Epstein–barr virus vaccines

2015

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Epstein–Barr virus (EBV) is the primary cause of infectious mononucleosis (IM) and is associated with epithelial cell malignancies such as nasopharyngeal carcinoma and gastric carcinoma, as well as lymphoid malignancies including Hodgkin lymphoma, Burkitt lymphoma, non-Hodgkin lymphoma and post-transplant lymphoproliferative disorder. EBV vaccines to prevent primary infection or disease, or therapeutic vaccines to treat EBV malignancies have not been licensed. Most efforts to develop prophylactic vaccines have focused on EBV gp350, which is the major target of neutralizing antibody. A single phase 2 trial of an EBV gp350 vaccine has been reported; the vaccine reduced the rate of IM but not virus infection. The observation that infusion of EBV-specific T cells can reduce disease due to Hodgkin lymphoma and nasopharyngeal carcinoma provides a proof of principle that a therapeutic vaccine for these and other EBV-associated malignancies might be effective. Most therapeutic vaccines have targeted EBV LMP2 and EBV nuclear antigen-1. As EBV is associated with nearly 200 000 new malignancies each year worldwide, an EBV vaccine to prevent these diseases is needed.

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Section: Ebv Glycoproteinsmentioning

confidence: 99%

Epstein–barr virus vaccines

2015

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“…The overall conserved character of the BARF1 gene suggests the importance of BARF1 function for virus-driven immortalization and escape strategies in an epithelial context. This is in line with the low variability of other lytic cycle proteins, like the viral IL10 encoded in BCRF1 [48] and the major envelope protein gp350/220 encoded in BLLF1 [49]. The limited overall sequence diverged at the protein level in different EBV isolates suggests BARF1 to play an important role in epithelial persistence during natural viral infection in man.…”

Section: Discussionmentioning

confidence: 61%

Conserved mutation of Epstein-Barr virus-encoded BamHI-A Rightward Frame-1 (BARF1) gene in Indonesian nasopharyngeal carcinoma

Hutajulu

Hoebe

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et al. 2010

Infect Agents Cancer

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BackgroundBamHI-A rightward frame-1 (BARF1) is a carcinoma-specific Epstein-Barr virus (EBV) encoded oncogene. Here we describe the BARF1 sequence diversity in nasopharyngeal carcinoma (NPC), other EBV-related diseases and Indonesian healthy EBV carriers in relation to EBV genotype, viral load and serology markers. Nasopharyngeal brushings from 56 NPC cases, blood or tissue from 15 other EBV-related disorders, spontaneous B cell lines (LCL) from 5 Indonesian healthy individuals and several prototype EBV isolates were analysed by PCR-direct sequencing.ResultsMost NPC isolates revealed specific BARF1 nucleotide changes compared to prototype B95-8 virus. At the protein level these mutations resulted in 3 main substitutions (V29A, W72G, H130R), which are not considered to cause gross tertiary structure alterations in the hexameric BARF1 protein. At least one amino acid conversion was detected in 80.3% of NPC samples compared to 33.3% of non-NPC samples (p < 0.001) and 40.0% of healthy LCLs (p = 0.074). NPC isolates also showed more frequent codon mutation than non-NPC samples. EBV strain typing revealed most isolates as EBV type 1. The viral load of either NPC or non-NPC samples was high, but only in non- NPC group it related to a particular BARF1 variant. Serology on NPC sera using IgA/EBNA-1 ELISA, IgA/VCA-p18 ELISA and immunoblot score showed no relation with BARF1 sequence diversity (p = 0.802, 0.382 and 0.058, respectively). NPC patients had variable antibody reactivity against purified hexameric NPC-derived BARF1 irrespective of the endogenous BARF1 sequence.ConclusionThe sequence variation of BARF1 observed in Indonesian NPC patients and controls may reflect a natural selection of EBV strains unlikely to be predisposing to carcinogenesis. The conserved nature of BARF1 may reflect an important role in EBV (epithelial) persistence.

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“…The late lytic cycle gene gp350 encodes a surface glycoprotein on the EBV particle which is the target of neutralizing antibodies for EBV infection. Sequence variation of this protein has been identified but again appears to show geographic restriction rather than tumor specific polymorphism [ 139 , 140 ].…”

Section: Lytic Cyclementioning

confidence: 99%

Epstein-Barr Virus Sequence Variation—Biology and Disease

2012

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Some key questions in Epstein-Barr virus (EBV) biology center on whether naturally occurring sequence differences in the virus affect infection or EBV associated diseases. Understanding the pattern of EBV sequence variation is also important for possible development of EBV vaccines. At present EBV isolates worldwide can be grouped into Type 1 and Type 2, a classification based on the EBNA2 gene sequence. Type 1 EBV is the most prevalent worldwide but Type 2 is common in parts of Africa. Type 1 transforms human B cells into lymphoblastoid cell lines much more efficiently than Type 2 EBV. Molecular mechanisms that may account for this difference in cell transformation are now becoming clearer. Advances in sequencing technology will greatly increase the amount of whole EBV genome data for EBV isolated from different parts of the world. Study of regional variation of EBV strains independent of the Type 1/Type 2 classification and systematic investigation of the relationship between viral strains, infection and disease will become possible. The recent discovery that specific mutation of the EBV EBNA3B gene may be linked to development of diffuse large B cell lymphoma illustrates the importance that mutations in the virus genome may have in infection and human disease.

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The evolution of Epstein-Barr virus inferred from the conservation and mutation of the virus glycoprotein gp350/220 gene

Cited by 11 publications

References 46 publications

Epstein–barr virus vaccines

Epstein–barr virus vaccines

Conserved mutation of Epstein-Barr virus-encoded BamHI-A Rightward Frame-1 (BARF1) gene in Indonesian nasopharyngeal carcinoma

Epstein-Barr Virus Sequence Variation—Biology and Disease

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