Dual impact of EZH1/2-targeted therapy in HTLV-1-associated inflammation: Direct and indirect mechanisms
Abstract
Human T cell leukemia virus type 1 (HTLV-1)-associated inflammation, including uveitis, lacks effective targeted therapies. Here, we investigated whether epigenetic modulation through EZH1/2 inhibition could influence HTLV-1-related ocular inflammation using in vitro co-culture and infection models. HTLV-1 exposure increased EZH1 and EZH2 expression and the repressive histone mark H3K27me3 in retinal pigment epithelial cells. Treatment with the dual EZH1/2 inhibitor valemetostat reduced H3K27me3 levels. Valemetostat showed limited effects on cell viability and induced only modest, context-dependent apoptosis. Virological analyses showed model-dependent changes in proviral load, accompanied by reduced viral gene expression. Profiling of cytokines and chemokines revealed context-dependent modulation of inflammatory mediators. Functional assessment using p65 nuclear translocation assays indicated partial attenuation of NF-κB activation under inflammatory stimulation. Collectively, these findings suggest that EZH1/2-mediated epigenetic regulation is primarily involved in HTLV-1-related inflammatory responses, and that inhibiting EZH1/2 may be a potential approach to modulate inflammatory signaling.
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BibTeX
@article{zou2026dual,
title = {{Dual impact of EZH1/2-targeted therapy in HTLV-1-associated inflammation: Direct and indirect mechanisms}},
author = {Yaru Zou and Koju Kamoi and Mingming Yang and Yuan Zong and Jing Zhang and Kyoko Ohno-Matsui},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117775},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03156-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dual impact of EZH1/2-targeted therapy in HTLV-1-associated inflammation: Direct and indirect mechanisms
AU - Yaru Zou
AU - Koju Kamoi
AU - Mingming Yang
AU - Yuan Zong
AU - Jing Zhang
AU - Kyoko Ohno-Matsui
PY - 2026
DA - 2026/10/08
JO - iScience
DO - 10.1016/j.isci.2026.117775
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03156-1
AB - Human T cell leukemia virus type 1 (HTLV-1)-associated inflammation, including uveitis, lacks effective targeted therapies. Here, we investigated whether epigenetic modulation through EZH1/2 inhibition could influence HTLV-1-related ocular inflammation using in vitro co-culture and infection models. HTLV-1 exposure increased EZH1 and EZH2 expression and the repressive histone mark H3K27me3 in retinal pigment epithelial cells. Treatment with the dual EZH1/2 inhibitor valemetostat reduced H3K27me3 levels. Valemetostat showed limited effects on cell viability and induced only modest, context-dependent apoptosis. Virological analyses showed model-dependent changes in proviral load, accompanied by reduced viral gene expression. Profiling of cytokines and chemokines revealed context-dependent modulation of inflammatory mediators. Functional assessment using p65 nuclear translocation assays indicated partial attenuation of NF-κB activation under inflammatory stimulation. Collectively, these findings suggest that EZH1/2-mediated epigenetic regulation is primarily involved in HTLV-1-related inflammatory responses, and that inhibiting EZH1/2 may be a potential approach to modulate inflammatory signaling.
SN - 2589-0042
ER -