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

doi:10.1038/375685a0

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 journal › Letter › peer-review

705 Scopus citations

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 carriers^{1, 2}, and is the only viral protein regularly detected in all malignancies associated with EBV^{3, 4}. Major histocompatibility complex (MHC) class I-restricted, EBNA1-specific cytotoxic T lymphocyte (CTL) responses have not been demonstrated^{3, 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 language	English
Pages (from-to)	685-688
Number of pages	4
Journal	Nature
Volume	375
Issue number	6533
DOIs	https://doi.org/10.1038/375685a0
State	Published - Jun 1995
Externally published	Yes

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@article{c0b17810753845cd8492c24d28d67851,

title = "Inhibition of antigen processing by the internal repeat region of the epstein-barr virus nuclear antigen-1",

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.",

author = "Jelena Levitskaya and Michael Coram and Victor Levitsky and Stefan Imreh and Steigerwald-Mullen, \{Patty M.\} and George Klein and Kurilla, \{Michael G.\} and Masucci, \{Maria G.\}",

year = "1995",

month = jun,

doi = "10.1038/375685a0",

language = "English",

volume = "375",

pages = "685--688",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "6533",

}

TY - JOUR

T1 - Inhibition of antigen processing by the internal repeat region of the epstein-barr virus nuclear antigen-1

AU - Levitskaya, Jelena

AU - Coram, Michael

AU - Levitsky, Victor

AU - Imreh, Stefan

AU - Steigerwald-Mullen, Patty M.

AU - Klein, George

AU - Kurilla, Michael G.

AU - Masucci, Maria G.

PY - 1995/6

Y1 - 1995/6

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/0029003999

U2 - 10.1038/375685a0

DO - 10.1038/375685a0

M3 - Letter

C2 - 7540727

AN - SCOPUS:0029003999

SN - 0028-0836

VL - 375

SP - 685

EP - 688

JO - Nature

JF - Nature

IS - 6533

ER -

Inhibition of antigen processing by the internal repeat region of the epstein-barr virus nuclear antigen-1

Abstract

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