biostudies-literatureIslam SNCI NIH HHSNational Institutes of HealthNIH HHS1406https://www.ebi.ac.uk/biostudies/studies/S-EPMC8310324biostudies-literatureUnknown13(7)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-posVirusesTargeting JAK/STAT Signaling Antagonizes Resistance to Oncolytic Reovirus Therapy Driven by Prior Infection with HTLV-1 in Models of T-Cell Lymphoma.PMC8310324R41 CA271967P30CA023074R01CA172443R01CA190789R01 CA190789Islam SEspitia CMCarew JSNawrocki STPersky DOfalseTargeting JAK/STAT Signaling Antagonizes Resistance to Oncolytic Reovirus Therapy Driven by Prior Infection with HTLV-1 in Models of T-Cell Lymphoma.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-pos2021-01-01T00:00:00Z2021 Jul2025-04-19T02:48:39.825Z2022-02-11T06:24:53.776ZS-EPMC83103243437261210.3390/v13071406