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Immunol."],"abstract":"<jats:p>The viral transactivator Tax plays a key role in HTLV-1 reactivation and <jats:italic>de novo<\/jats:italic> infection. Previous approaches focused on the histone deacetylase inhibitor (HDACi) Valproate as a latency-reversing agent to boost Tax expression and expose infected cells to the host\u2019s immune response. However, following treatment with Valproate proviral load decreases in patients with HAM\/TSP were only transient. Here, we hypothesize that other compounds, including more potent and selective HDACi, might prove superior to Valproate in manipulating Tax expression. Thus, a panel of HDACi (Vorinostat\/SAHA\/Zolinza, Panobinostat\/LBH589\/Farydak, Belinostat\/PXD101\/Beleodaq, Valproate, Entinostat\/MS-275, Romidepsin\/FK228\/Istodax, and MC1568) was selected and tested for toxicity and potency in enhancing Tax expression. The impact of the compounds was evaluated in different model systems, including transiently transfected T-cells, chronically HTLV-1-infected T-cell lines, and freshly isolated PBMCs from HTLV-1 carriers <jats:italic>ex vivo<\/jats:italic>. We identified the pan-HDACi Panobinostat and class I HDACi Romidepsin as particularly potent agents at raising Tax expression. qRT-PCR analysis revealed that these inhibitors considerably boost <jats:italic>tax<\/jats:italic> and Tax-target gene transcription. However, despite this significant increase in <jats:italic>tax<\/jats:italic> transcription and histone acetylation, protein levels of Tax were only moderately enhanced. In conclusion, these data demonstrate the ability of Panobinostat and Romidepsin to manipulate Tax expression and provide a foundation for further research into eliminating latently infected cells. These findings also contribute to a better understanding of conditions limiting transcription and translation of viral gene products.<\/jats:p>","DOI":"10.3389\/fimmu.2022.978800","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T05:00:05Z","timestamp":1660626005000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["HDAC inhibitors Panobinostat and Romidepsin enhance tax transcription in HTLV-1-infected cell lines and freshly isolated patients\u2019 T-cells"],"prefix":"10.3389","volume":"13","author":[{"given":"Annika P.","family":"Schnell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Kohrt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aris","family":"Aristodemou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham P.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R. 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