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Journal of Virology, January 2009, p. 273-282, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01532-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Reduction in RNA Levels Rather than Retardation of Translation Is Responsible for the Inhibition of Major Histocompatibility Complex Class I Antigen Presentation by the Glutamic Acid-Rich Repeat of Herpesvirus Saimiri Open Reading Frame 73 {triangledown}

Jiayu Gao,1,{dagger} Judy M. Coulson,2 Adrian Whitehouse,3 and Neil Blake1*

School of Infection and Host Defence, University of Liverpool, Liverpool L69 3GA, United Kingdom,1 School of Biomedical Sciences, University of Liverpool, Liverpool L69 3BX, United Kingdom,2 Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom3

Received 21 July 2008/ Accepted 15 October 2008

Herpesvirus saimiri (HVS) establishes a persistent infection in squirrel monkeys by maintaining its episome within T lymphocytes. The product of open reading frame 73 (ORF73) plays a key role in episomal maintenance and is the functional homologue of Epstein-Barr virus EBNA1 and Kaposi's sarcoma-associated herpesvirus LANA1 proteins. There is little sequence homology among these proteins, although all contain a central domain of repeating amino acids. The repeat domains of EBNA1 and LANA1 enhance the stability of these proteins and cause a retardation in self-protein synthesis, leading to poor recognition by CD8+ cytotoxic T lymphocytes (CTL). The HVS ORF73 repeat domain is composed of a glutamic acid and glycine repeat linked to a glutamic acid and alanine repeat (EG-EA repeat). Here we show that the EG-EA repeat similarly causes a reduction in the recognition of ORF73 by CD8+ CTL. However, deletion of the EG-EA repeat from HVS ORF73 had no affect on the stability of the protein or its rate of translation. In contrast, the presence of the EG-EA repeat was found to decrease the steady-state levels of ORF73 mRNA. The inhibitory properties of the EG-EA repeat were maintained when transferred to a heterologous protein, and manipulation of the repeat revealed that the motif EEAEEAEEE was sufficient to cause a reduction in recognition of ORF73 by CD8+ CTL. Thus, the EG-EA repeat of HVS ORF73 plays a role in immune evasion but utilizes a mechanism distinct from that of the EBNA1 and LANA1 repeats.

* Corresponding author. Mailing address: Division of Medical Microbiology, University of Liverpool, 8th Floor Duncan Building, Daulby Street, Liverpool L69 3GA, United Kingdom. Phone: 44-151-706-4386. Fax: 44-151-706-5805. E-mail: nwblake{at}liv.ac.uk

{triangledown} Published ahead of print on 22 October 2008.

{dagger} Present address: School of Health and Bioscience, University of East London, London E15 4LZ, United Kingdom.

Journal of Virology, January 2009, p. 273-282, Vol. 83, No. 1
0022-538X/09/$08.00+0     doi:10.1128/JVI.01532-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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