Antigenic and sequence variation in the C-terminal unique domain of the Epstein-Barr virus nuclear antigen EBNA-1.

2.50
Hdl Handle:
http://hdl.handle.net/10541/97967
Title:
Antigenic and sequence variation in the C-terminal unique domain of the Epstein-Barr virus nuclear antigen EBNA-1.
Authors:
Wrightham, Mark N; Stewart, James P; Janjua, Nusrat J; Pepper, Stuart D; Sample, C; Rooney, Claire M; Arrand, John R
Abstract:
The Epstein-Barr virus (EBV) nuclear antigen EBNA-1 is essential for viral genome maintenance in vitro and may be the only EBV protein expressed by the majority of latently infected cells in vivo. EBNA-1 may therefore be critical to the evasion of host immunity which allows persistent infection. EBNA-1 includes a polymorphic internal repeat domain of unknown significance and unique regions which mediate all known functional activities and which have hitherto been assumed to be conserved between strains. Monoclonal antibodies were generated using a construct based on EBNA-1 of the prototype B95-8 strain, deleted for the repeat domain. These antibodies showed a limited profile of recognition of EBNA-1 in common laboratory EBV+ cell lines by immunoprecipitation and immunostaining. The observed antigenic heterogeneity also extended to spontaneously transformed B lymphoblastoid cell lines (LCLs) representing viral isolates circulating within US and UK populations. DNA fragments spanning the C-terminal unique domain of EBNA-1 from eleven spontaneous LCLs were amplified by polymerase chain reaction for sequencing, which directly demonstrated extensive and unexpected variability between diverse type 1 EBV isolates. The resulting polymorphism affects most of the putative MHC Class I binding epitopes which could be identified within this region using published sequence motifs, and influences MHC binding by variants of at least one such peptide in the processing mutant cell line T2. These findings could be related to the apparent lack of recognition of EBNA-1 by cytotoxic T lymphocytes.
Affiliation:
Department of Molecular Biology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, United Kingdom.
Citation:
Antigenic and sequence variation in the C-terminal unique domain of the Epstein-Barr virus nuclear antigen EBNA-1. 1995, 208 (2):521-30 Virology
Journal:
Virology
Issue Date:
20-Apr-1995
URI:
http://hdl.handle.net/10541/97967
DOI:
10.1006/viro.1995.1183
PubMed ID:
7538250
Type:
Article
Language:
en
ISSN:
0042-6822
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorWrightham, Mark Nen
dc.contributor.authorStewart, James Pen
dc.contributor.authorJanjua, Nusrat Jen
dc.contributor.authorPepper, Stuart Den
dc.contributor.authorSample, Cen
dc.contributor.authorRooney, Claire Men
dc.contributor.authorArrand, John Ren
dc.date.accessioned2010-05-05T11:02:42Z-
dc.date.available2010-05-05T11:02:42Z-
dc.date.issued1995-04-20-
dc.identifier.citationAntigenic and sequence variation in the C-terminal unique domain of the Epstein-Barr virus nuclear antigen EBNA-1. 1995, 208 (2):521-30 Virologyen
dc.identifier.issn0042-6822-
dc.identifier.pmid7538250-
dc.identifier.doi10.1006/viro.1995.1183-
dc.identifier.urihttp://hdl.handle.net/10541/97967-
dc.description.abstractThe Epstein-Barr virus (EBV) nuclear antigen EBNA-1 is essential for viral genome maintenance in vitro and may be the only EBV protein expressed by the majority of latently infected cells in vivo. EBNA-1 may therefore be critical to the evasion of host immunity which allows persistent infection. EBNA-1 includes a polymorphic internal repeat domain of unknown significance and unique regions which mediate all known functional activities and which have hitherto been assumed to be conserved between strains. Monoclonal antibodies were generated using a construct based on EBNA-1 of the prototype B95-8 strain, deleted for the repeat domain. These antibodies showed a limited profile of recognition of EBNA-1 in common laboratory EBV+ cell lines by immunoprecipitation and immunostaining. The observed antigenic heterogeneity also extended to spontaneously transformed B lymphoblastoid cell lines (LCLs) representing viral isolates circulating within US and UK populations. DNA fragments spanning the C-terminal unique domain of EBNA-1 from eleven spontaneous LCLs were amplified by polymerase chain reaction for sequencing, which directly demonstrated extensive and unexpected variability between diverse type 1 EBV isolates. The resulting polymorphism affects most of the putative MHC Class I binding epitopes which could be identified within this region using published sequence motifs, and influences MHC binding by variants of at least one such peptide in the processing mutant cell line T2. These findings could be related to the apparent lack of recognition of EBNA-1 by cytotoxic T lymphocytes.en
dc.language.isoenen
dc.subject.meshAmino Acid Sequence-
dc.subject.meshAntibodies, Monoclonal-
dc.subject.meshAntibodies, Viral-
dc.subject.meshAntigenic Variation-
dc.subject.meshAntigens, Viral-
dc.subject.meshB-Lymphocytes-
dc.subject.meshBase Sequence-
dc.subject.meshCell Line, Transformed-
dc.subject.meshDNA, Viral-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshEpitopes-
dc.subject.meshEpstein-Barr Virus Nuclear Antigens-
dc.subject.meshGenetic Variation-
dc.subject.meshHLA-A2 Antigen-
dc.subject.meshHerpesvirus 4, Human-
dc.subject.meshHumans-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshRecombinant Fusion Proteins-
dc.subject.meshSequence Analysis, DNA-
dc.subject.meshT-Lymphocytes-
dc.titleAntigenic and sequence variation in the C-terminal unique domain of the Epstein-Barr virus nuclear antigen EBNA-1.en
dc.typeArticleen
dc.contributor.departmentDepartment of Molecular Biology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, United Kingdom.en
dc.identifier.journalVirologyen
All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.