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dc.contributor.authorTellam, Judy T*
dc.contributor.authorLekieffre, Lea*
dc.contributor.authorZhong, Jie*
dc.contributor.authorLynn, David J*
dc.contributor.authorKhanna, Rajiv*
dc.date.accessioned2013-02-28T15:39:11Z
dc.date.available2013-02-28T15:39:11Z
dc.date.issued2012-12-27
dc.identifier.citationTellam JT, Lekieffre L, Zhong J, Lynn DJ, Khanna R (2012) Messenger RNA Sequence Rather than Protein Sequence Determines the Level of Self-synthesis and Antigen Presentation of the EBV-encoded Antigen, EBNA1. PLoS Pathog 8(12): e1003112. doi:10.1371/journal.ppat.1003112en_GB
dc.identifier.issn1553-7366
dc.identifier.urihttp://hdl.handle.net/11019/335
dc.descriptionpeer-revieweden_GB
dc.description.abstractViruses establishing persistent latent infections have evolved various mechanisms to avoid immune surveillance. The Epstein-Barr virus-encoded nuclear antigen, EBNA1, expressed in all EBV-associated malignancies, modulates its own protein levels at quantities sufficient to maintain viral infection but low enough so as to minimize an immune response by the infected host cell. This evasion mechanism is regulated through an internal purine-rich mRNA repeat sequence encoding glycine and alanine residues. In this study we assess the impact of the repeat's nucleotide versus peptide sequence on inhibiting EBNA1 self-synthesis and antigen presentation. We demonstrate that altered peptide sequences resulting from frameshift mutations within the repeat do not alleviate the immune-evasive function of EBNA1, suggesting that the repetitive purine-rich mRNA sequence itself is responsible for inhibiting EBNA1 synthesis and subsequent poor immunogenicity. Our comparative analysis of the mRNA sequences of the corresponding repeat regions of different gammaherpesvirus maintenance homologues to EBNA1 highlights the high degree of identity between the nucleotide sequences despite very little homology in the encoded amino acid sequences. These studies demonstrate the importance of gammaherpesvirus purine-rich mRNA repeat sequences on antigenic epitope generation and evasion from T-cell mediated immune control, suggesting novel approaches to prevention and treatment of latent infection by this class of virus.en_GB
dc.description.sponsorshipNational Health & Medical Research Council (NH&MRC) Canberra, Australia (#496684 APP1005091); NH&MRC Career Development Award Research Fellowship (#496712)en_GB
dc.language.isoenen_GB
dc.publisherPLOSen_GB
dc.relation.ispartofseriesPLoS Pathogens;vol 8
dc.subjectEpstein-Barr-Virusen_GB
dc.subjectSarcoma-Associated Herpesvirusen_GB
dc.subjectT-Cell Recognitionen_GB
dc.subjectOpen Reading Frameen_GB
dc.subjectNuclear Antigen-1en_GB
dc.subjectKaposis-Sarcomaen_GB
dc.subjectSimian Homologsen_GB
dc.subjectImmune Evasionen_GB
dc.subjectEndogenous Presentationen_GB
dc.subjectViral Evasionen_GB
dc.titleMessenger RNA Sequence Rather than Protein Sequence Determines the Level of Self-synthesis and Antigen Presentation of the EBV-encoded Antigen, EBNA1en_GB
dc.typeArticleen_GB
dc.identifier.doihttp://dx.doi.org/10.1371/journal.ppat.1003112
dc.contributor.sponsorNational Health & Medical Research Council Australia
dc.contributor.sponsorGrantNumber496684 APP1005091
dc.contributor.sponsorGrantNumber496712
refterms.dateFOA2018-01-12T07:49:23Z


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