Reactivation in B-cells is critical for the Epstein Barr virus (EBV) life cycle and it plays a role in amplifying viral titers in AIDS patients. The repertoire of EBV genes thought to be involved in viral replication consists primarily of approximately 80-90 protein-coding genes. These viral proteins play very diverse roles in virus production including roles in DNA replication, RNA transcription, molecular trafficking, virion assembly, viral egress, host shut-off etc. This is not to mention roles as viron components;both components that form the virus architecture as well as those that are involved in inducing the rapid signaling responses immediately following new infection. We hypothesize that in addition to this group of known protein coding genes, EBV encodes a previously unappreciated group of long non-coding transcripts that will ultimately be found to play an equally diverse set of functions in virus replication. Conceptually this would be important because it would change the texture and the details of how most of us visualize the reactivation process. From a practical standpoint, it would give us a new class of molecular targets that may offer the application of alternative therapeutic approaches against EBV.

Public Health Relevance

The replication phase of the Epstein Barr virus results in the production of infectious virions and the spread of the virus within the host. In AIDS patients, virl proteins produced during the replication phase as well as oncogenic latency proteins are not as well targeted by the immune system, resulting in additional pathogenic consequences including lymphomas. Here we propose a new regulatory model for how EBV facilitates progression through the viral replication phase.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI106676-01A1
Application #
8750146
Study Section
Special Emphasis Panel (ZRG1-AARR-K (02))
Program Officer
Beisel, Christopher E
Project Start
2014-02-18
Project End
2019-01-31
Budget Start
2014-02-18
Budget End
2015-01-31
Support Year
1
Fiscal Year
2014
Total Cost
$376,250
Indirect Cost
$126,250
Name
Tulane University
Department
Pathology
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
O'Grady, Tina; Wang, Xia; Höner Zu Bentrup, Kerstin et al. (2016) Global transcript structure resolution of high gene density genomes through multi-platform data integration. Nucleic Acids Res 44:e145
Liu, Yao-Zhong; Roy-Engel, Astrid M; Baddoo, Melody C et al. (2016) The impact of oil spill to lung health--Insights from an RNA-seq study of human airway epithelial cells. Gene 578:38-51
Yin, Qinyan; Wang, Xia; Roberts, Claire et al. (2016) Methylation status and AP1 elements are involved in EBV-mediated miR-155 expression in EBV positive lymphoma cells. Virology 494:158-67
Zhou, Xiang; Hao, Qian; Liao, Peng et al. (2016) Nerve growth factor receptor negates the tumor suppressor p53 as a feedback regulator. Elife 5:
Zhan, Yang; Zhang, Guanyi; Wang, Xiaojie et al. (2016) Interplay Between Cytoplasmic and Nuclear Androgen Receptor Splice Variants Mediate Castration Resistance. Mol Cancer Res :
Lin, Zhen; Swan, Kenneth; Zhang, Xin et al. (2016) Secreted Oral Epithelial Cell Membrane Vesicles Induce Epstein-Barr Virus Reactivation in Latently Infected B Cells. J Virol 90:3469-79
Deininger, Prescott; Morales, Maria E; White, Travis B et al. (2016) A comprehensive approach to expression of L1 loci. Nucleic Acids Res :
Strong, Michael J; Blanchard 4th, Eugene; Lin, Zhen et al. (2016) A comprehensive next generation sequencing-based virome assessment in brain tissue suggests no major virus - tumor association. Acta Neuropathol Commun 4:71
Kim, Jung-Hyun; Baddoo, Melody C; Park, Eun Young et al. (2016) SON and Its Alternatively Spliced Isoforms Control MLL Complex-Mediated H3K4me3 and Transcription of Leukemia-Associated Genes. Mol Cell 61:859-73
Dai, Lu; Bai, Lihua; Lin, Zhen et al. (2016) Transcriptomic analysis of KSHV-infected primary oral fibroblasts: The role of interferon-induced genes in the latency of oncogenic virus. Oncotarget 7:47052-47060

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