{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:50:42Z","timestamp":1792612242537,"version":"4.5.0"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"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":["R01CA190789"],"award-info":[{"award-number":["R01CA190789"]}],"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":["R01CA172443"],"award-info":[{"award-number":["R01CA172443"]}],"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":["P30CA023074"],"award-info":[{"award-number":["P30CA023074"]}],"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 retrovirus that infects at least 10 million people worldwide and is associated with the development of T-cell lymphoma (TCL). The treatment of TCL remains challenging and new treatment options are urgently needed. With the goal of developing a novel therapeutic approach for TCL, we investigated the activity of the clinical formulation of oncolytic reovirus (Reolysin, Pelareorep) in TCL models. Our studies revealed that HTLV-1-negative TCL cells were highly sensitive to Reolysin-induced cell death, but HTLV-1-positive TCL cells were resistant. Consistent with these data, reovirus displayed significant viral accumulation in HTLV-1-negative cells, but failed to efficiently replicate in HTLV-1-positive cells. Transcriptome analyses of HTLV-1-positive vs. negative cells revealed a significant increase in genes associated with retroviral infection including interleukin-13 and signal transducer and activator of transcription 5 (STAT5). To investigate the relationship between HTLV-1 status and sensitivity to Reolysin, we infected HTLV-1-negative cells with HTLV-1. The presence of HTLV-1 resulted in significantly decreased sensitivity to Reolysin. Treatment with the JAK inhibitor ruxolitinib suppressed STAT5 phosphorylation and expression of the key anti-viral response protein MX1 and enhanced the anti-TCL activity of Reolysin in both HTLV-1-positive and negative cells. Our data demonstrate that the inhibition of the JAK\/STAT pathway can be used as a novel approach to antagonize the resistance of HTLV-1-positive cells to oncolytic virus therapy.<\/jats:p>","DOI":"10.3390\/v13071406","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T05:10:59Z","timestamp":1626757859000},"page":"1406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Targeting JAK\/STAT Signaling Antagonizes Resistance to Oncolytic Reovirus Therapy Driven by Prior Infection with HTLV-1 in Models of T-Cell Lymphoma"],"prefix":"10.3390","volume":"13","author":[{"given":"Shariful","family":"Islam","sequence":"first","affiliation":[{"name":"Division of Translational and Regenerative Medicine, Department of Medicine, The University of Arizona Cancer Center, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia M.","family":"Espitia","sequence":"additional","affiliation":[{"name":"Division of Translational and Regenerative Medicine, Department of Medicine, The University of Arizona Cancer Center, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel O.","family":"Persky","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine, The University of Arizona Cancer Center, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Carew","sequence":"additional","affiliation":[{"name":"Division of Translational and Regenerative Medicine, Department of Medicine, The University of Arizona Cancer Center, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffan T.","family":"Nawrocki","sequence":"additional","affiliation":[{"name":"Division of Translational and Regenerative Medicine, Department of Medicine, The University of Arizona Cancer Center, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"El Hajj, H., Tsukasaki, K., Cheminant, M., Bazarbachi, A., Watanabe, T., and Hermine, O. 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