Next Article in Journal
MicroRNA and Pathogenesis of Enterovirus Infection
Next Article in Special Issue
Molecular Studies of HTLV-1 Replication: An Update
Previous Article in Journal
Human Cytomegalovirus Inhibits the PARsylation Activity of Tankyrase—A Potential Strategy for Suppression of the Wnt Pathway
Previous Article in Special Issue
HTLV-1, Immune Response and Autoimmunity
Article Menu

Export Article

Open AccessArticle
Viruses 2016, 8(1), 7; doi:10.3390/v8010007

PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival

1
Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA
2
Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA
3
Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210, USA
4
Department of Microbiology and Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA
5
Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA
6
Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Louis M. Mansky
Received: 6 October 2015 / Revised: 11 December 2015 / Accepted: 18 December 2015 / Published: 30 December 2015
(This article belongs to the Special Issue Recent Advances in HTLV Research 2015)
View Full-Text   |   Download PDF [2200 KB, uploaded 30 December 2015]   |  

Abstract

Human T-cell leukemia virus type-1 (HTLV-1) is a tumorigenic retrovirus responsible for development of adult T-cell leukemia/lymphoma (ATLL). This disease manifests after a long clinical latency period of up to 2–3 decades. Two viral gene products, Tax and HBZ, have transforming properties and play a role in the pathogenic process. Genetic and epigenetic cellular changes also occur in HTLV-1-infected cells, which contribute to transformation and disease development. However, the role of cellular factors in transformation is not completely understood. Herein, we examined the role of protein arginine methyltransferase 5 (PRMT5) on HTLV-1-mediated cellular transformation and viral gene expression. We found PRMT5 expression was upregulated during HTLV-1-mediated T-cell transformation, as well as in established lymphocytic leukemia/lymphoma cell lines and ATLL patient PBMCs. shRNA-mediated reduction in PRMT5 protein levels or its inhibition by a small molecule inhibitor (PRMT5i) in HTLV-1-infected lymphocytes resulted in increased viral gene expression and decreased cellular proliferation. PRMT5i also had selective toxicity in HTLV-1-transformed T-cells. Finally, we demonstrated that PRMT5 and the HTLV-1 p30 protein had an additive inhibitory effect on HTLV-1 gene expression. Our study provides evidence for PRMT5 as a host cell factor important in HTLV-1-mediated T-cell transformation, and a potential target for ATLL treatment. View Full-Text
Keywords: HTLV-1; PRMT5; transformation; ATLL; Tax; HBZ; p30; lymphoma HTLV-1; PRMT5; transformation; ATLL; Tax; HBZ; p30; lymphoma
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Panfil, A.R.; Al-Saleem, J.; Howard, C.M.; Mates, J.M.; Kwiek, J.J.; Baiocchi, R.A.; Green, P.L. PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival. Viruses 2016, 8, 7.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top