PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival
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...
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MDPI AG
2015-12-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/8/1/7 |
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| author | Amanda R. Panfil Jacob Al-Saleem Cory M. Howard Jessica M. Mates Jesse J. Kwiek Robert A. Baiocchi Patrick L. Green |
| author_facet | Amanda R. Panfil Jacob Al-Saleem Cory M. Howard Jessica M. Mates Jesse J. Kwiek Robert A. Baiocchi Patrick L. Green |
| author_sort | Amanda R. Panfil |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T11:37:09Z |
| format | Article |
| id | doaj.art-11bc1fea87494619b1b5f628a7d71b91 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-10T11:37:09Z |
| publishDate | 2015-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-11bc1fea87494619b1b5f628a7d71b912022-12-22T01:50:23ZengMDPI AGViruses1999-49152015-12-0181710.3390/v8010007v8010007PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell SurvivalAmanda R. Panfil0Jacob Al-Saleem1Cory M. Howard2Jessica M. Mates3Jesse J. Kwiek4Robert A. Baiocchi5Patrick L. Green6Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USACenter for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USACenter for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USACenter for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210, USACenter for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USADivision of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USACenter for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USAHuman 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.http://www.mdpi.com/1999-4915/8/1/7HTLV-1PRMT5transformationATLLTaxHBZp30lymphoma |
| spellingShingle | Amanda R. Panfil Jacob Al-Saleem Cory M. Howard Jessica M. Mates Jesse J. Kwiek Robert A. Baiocchi Patrick L. Green PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival Viruses HTLV-1 PRMT5 transformation ATLL Tax HBZ p30 lymphoma |
| title | PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival |
| title_full | PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival |
| title_fullStr | PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival |
| title_full_unstemmed | PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival |
| title_short | PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival |
| title_sort | prmt5 is upregulated in htlv 1 mediated t cell transformation and selective inhibition alters viral gene expression and infected cell survival |
| topic | HTLV-1 PRMT5 transformation ATLL Tax HBZ p30 lymphoma |
| url | http://www.mdpi.com/1999-4915/8/1/7 |
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