Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1

Jelena Levitskaya, Michael Coram, Victor Levitsky, Stefan Imreh, Patty M. Steigerwald-Mullen, George Klein, Michael G. Kurilla, Maria G. Masucci

Research output: Contribution to journalArticlepeer-review

Abstract

THE Epstein-Barr virus (EBV)-encoded nuclear antigen (EBNA1) is expressed in latently EBV-infected B lymphocytes that persist for life in healthy virus carriers1,2, and is the only viral protein regularly detected in all malignancies associated with EBV3,4. Major histocompatibility complex (MHC) class I-restricted, EBNA1-specific cytotoxic T lymphocyte (CTL) responses have not been demonstrated3,5. Using recombinant vaccinia viruses encoding chimaeric proteins containing an immunodominant human leukocyte antigen All-restricted CTL epitope, amino acids 416-424 of the EBNA4 protein6, inserted within the intact EBNA1, or within an EBNA1 deletion mutant devoid of the internal Gly-Ala repetitive sequence, we demonstrate that the Gly-Ala repeats generate a cis-acting inhibitory signal that interferes with antigen processing and MHC class I-restricted presentation. Insertion of the Gly-Ala repeats downstream of the 416-424 epitope inhibited CTL recognition of a chimaeric EBNA4 protein. The results highlight a previously unknown mechanism of viral escape from CTL surveillance, and support the view that the resistance of cells expressing EBNA1 to rejection mediated by CTL is a critical requirement for EBV persistence and pathogenesis.

Original languageEnglish (US)
Pages (from-to)685-688
Number of pages4
JournalNature
Volume375
Issue number6533
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • General

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