{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T19:26:52Z","timestamp":1782588412169,"version":"3.54.5"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2015,12,30]],"date-time":"2015-12-30T00:00:00Z","timestamp":1451433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI111125"],"award-info":[{"award-number":["AI111125"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CA100730"],"award-info":[{"award-number":["CA100730"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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\u20133 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.<\/jats:p>","DOI":"10.3390\/v8010007","type":"journal-article","created":{"date-parts":[[2015,12,30]],"date-time":"2015-12-30T10:25:05Z","timestamp":1451471105000},"page":"7","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["PRMT5 Is Upregulated in HTLV-1-Mediated T-Cell Transformation and Selective Inhibition Alters Viral Gene Expression and Infected Cell Survival"],"prefix":"10.3390","volume":"8","author":[{"given":"Amanda","family":"Panfil","sequence":"first","affiliation":[{"name":"Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Al-Saleem","sequence":"additional","affiliation":[{"name":"Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory","family":"Howard","sequence":"additional","affiliation":[{"name":"Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Mates","sequence":"additional","affiliation":[{"name":"Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse","family":"Kwiek","sequence":"additional","affiliation":[{"name":"Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Microbiology and Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Baiocchi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Green","sequence":"additional","affiliation":[{"name":"Center for Retrovirus Research, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6058","DOI":"10.1038\/sj.onc.1208968","article-title":"Global epidemiology of HTLV-I infection and associated diseases","volume":"24","author":"Proietti","year":"2005","journal-title":"Oncogene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1073\/pnas.77.12.7415","article-title":"Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma","volume":"77","author":"Poiesz","year":"1980","journal-title":"Proc. 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