Efficient Translation of Epstein-Barr Virus (EBV) DNA Polymerase Contributes to the Enhanced Lytic Replication Phenotype of M81 EBV
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Published:2018-03-15
Issue:6
Volume:92
Page:
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ISSN:0022-538X
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Container-title:Journal of Virology
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language:en
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Short-container-title:J Virol
Author:
Church Trenton Mel1, Verma Dinesh1, Thompson Jacob2, Swaminathan Sankar12ORCID
Affiliation:
1. Division of Infectious Diseases, Department of Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA 2. Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA
Abstract
ABSTRACT
Epstein-Barr virus (EBV) is linked to the development of both lymphoid and epithelial malignancies worldwide. The M81 strain of EBV, isolated from a Chinese patient with nasopharyngeal carcinoma (NPC), demonstrates spontaneous lytic replication and high-titer virus production in comparison to the prototype B95-8 EBV strain. Genetic comparisons of M81 and B95-8 EBVs were previously been performed in order to determine if the hyperlytic property of M81 is associated with sequence differences in essential lytic genes. EBV SM is an RNA-binding protein expressed during early lytic replication that is essential for virus production. We compared the functions of M81 SM and B95-8 SM and demonstrate that polymorphisms in SM do not contribute to the lytic phenotype of M81 EBV. However, the expression level of the EBV DNA polymerase protein was much higher in M81- than in B95-8-infected cells. The relative deficiency in the expression of B95-8 DNA polymerase was related to the B95-8 genome deletion, which truncates the BALF5 3′ untranslated region (UTR). Similarly, the insertion of bacmid DNA into the widely used recombinant B95-8 bacmid creates an inefficient BALF5 3′ UTR. We further showed that the while SM is required for and facilitates the efficient expression of both M81 and B95-8 mRNAs regardless of the 3′ UTR, the BALF5 3′ UTR sequence is important for BALF5 protein translation. These data indicate that the enhanced lytic replication and virus production of M81 compared to those of B95-8 are partly due to the robust translation of EBV DNA polymerase required for viral DNA replication due to a more efficient BALF5 3′ UTR in M81.
IMPORTANCE
Epstein-Barr virus (EBV) infects more than 90% of the human population, but the incidence of EBV-associated tumors varies greatly in different parts of the world. Thus, understanding the connection between genetic polymorphisms from patient isolates of EBV, gene expression phenotypes, and disease is important and may help in developing antiviral therapy. This study examines potential causes of the enhanced lytic replicative properties of M81 EBV isolated from a nasopharyngeal carcinoma (NPC) patient and provides new evidence for the role of the BALF5 gene 3′ UTR sequence in DNA polymerase protein expression during lytic replication. Variation in the gene structure of the DNA polymerase gene may therefore contribute to lytic virus reactivation and pathogenesis.
Funder
HHS | NIH | National Cancer Institute Office of Research and Development
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference43 articles.
1. Longnecker RM, Kieff E, Cohen JI. 2013. Epstein-Barr virus, p 1898–1959. In Knipe DM, Howley PM, Cohen JI, Griffin DE, Lamb RA, Martin MA, Racaniello VR, Roizman B (ed), Fields virology, 6th ed, vol 2. Lippincott Williams & Wilkins, Philadelphia, PA. 2. Rickinson AB, Kieff E. 2007. Epstein-Barr virus, p 2655–2700. In Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE (ed), Fields virology, 5th ed, vol 2. Lippincott Williams & Wilkins, Philadelphia, PA. 3. The extent of genetic diversity of Epstein-Barr virus and its geographic and disease patterns: A need for reappraisal 4. Epstein–Barr virus-associated malignancies: epidemiologic patterns and etiologic implications 5. Nasopharyngeal carcinoma (NPC). I. Types of cultures derived from tumour biopsies and non-tumorous tissues of chinese patients with special reference to lymphoblastoid transformation
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