Volume 11 Supplement 1

16th International Conference on Human Retroviruses: HTLV and Related Viruses

Open Access

Role of protein arginine methyltransferase 5 over-expression in HTLV-1-driven cellular transformation and leukemia

  • Amanda R Panfil1,
  • Jacob J Al-Saleem1,
  • Robert A Baiocchi2 and
  • Patrick L Green1Email author
Retrovirology201411(Suppl 1):O65

https://doi.org/10.1186/1742-4690-11-S1-O65

Published: 7 January 2014

Human T-cell leukemia virus -1 (HTLV-1) is a delta retrovirus that infects an estimated 15-25 million people worldwide. HTLV-1 is the causative infectious agent of adult T-cell leukemia/lymphoma (ATL) and a neurodegenerative disease (HAM/TSP). While the probability of presenting any symptoms related to HTLV-1 infection is relatively low (roughly 5-10% for the lifetime of an infected individual), the disease progression and prognosis of those infected individuals who develop ATL is fatal, with a median survival range of 8-10 months. Unfortunately, ATL is highly chemotherapy resistant and while many current therapies improve ATL patient survival, the patients consistently relapse. Therefore, a need exists to develop treatments that improve ATL outcome. We have recently identified PRMT5 (protein arginine methyltransferase 5) as a potential target to modulate HTLV-1 gene expression. We find that PRMT5 protein levels are elevated in T-cell leukemia/lymphoma cell lines compared to freshly isolated naïve T-cells. PRMT5 RNA levels do not correlate to PRMT5 protein levels, suggesting a possible post-transcriptional method of regulation. Furthermore, we also show that PRMT5 protein expression is slightly elevated during short-term immortalization, but gains highest expression after transformation and IL-2 independence. Utilizing shRNA vectors, we demonstrate that knockdown of endogenous PRMT5 results in a decrease in viral p19 production in a HTLV-1-transformed cell line. Finally, we observe a decrease in cell proliferation and in viral gene expression when HTLV-1-infected/-transformed cells are treated with a novel small molecule inhibitor of PRMT5. In conclusion, we find PRMT5 to be a positive regulator of HTLV-1 gene expression.

Authors’ Affiliations

(1)
Center for Retrovirus Research, Department of Veterinary Biosciences, Comprehensive Cancer Center and Solove Research Institute, The Ohio State University
(2)
Division of Hematology-Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University

Copyright

© Panfil et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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