{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:01:46Z","timestamp":1791511306601,"version":"4.3.4"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Prevention and Control of Emeging and Major Infectious Diseases-National Science and Technology Major Project","award":["2025ZD01904302"],"award-info":[{"award-number":["2025ZD01904302"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272316,82341072"],"award-info":[{"award-number":["82272316,82341072"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472264"],"award-info":[{"award-number":["82472264"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Key Laboratory of Molecular Virology, Jilin Province","award":["20102209"],"award-info":[{"award-number":["20102209"]}]},{"name":"The Science and Technology Department of Jilin Province","award":["YDZJ202401447ZYTS"],"award-info":[{"award-number":["YDZJ202401447ZYTS"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,6,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>HIV-1 Tat functions as a key transcriptional activator that amplifies viral transcription by recruiting host transcription elongation machinery, thereby forming a self-amplifying positive-feedback loop. Thus, cellular levels and post-translational modifications of Tat directly determine the efficiency of viral replication, as well as the establishment and reactivation of proviral latency. Elucidating the regulatory network that maintains Tat protein levels is therefore important for developing HIV cure strategies. Here, we identify the E3 ubiquitin ligase TRIP12 as a novel positive regulator of Tat stability that inhibits its proteasomal degradation. TRIP12 stabilizes Tat independently of its intrinsic E3 ligase activity by enhancing the interaction between the deubiquitinase USP7 and Tat, thereby reducing K48-linked ubiquitination of Tat, a modification typically associated with protein degradation. TRIP12 knockout significantly accelerates Tat degradation due to reduced USP7-Tat interaction, resulting in the suppression of viral transcription and impaired reactivation of latent virus. Moreover, TRIP12-mediated stabilization of Tat is consistently observed among multiple clade B HIV-1 strains tested in this study. Notably, TRIP12 mRNA levels are associated with plasma viral load and disease progression in people living with HIV, suggesting a potential clinical relevance of TRIP12 in HIV-1 pathogenesis. These findings expand our understanding of host-virus interactions and provide new insights into the molecular regulation of Tat stability, offering a potential basis for developing Tat-targeted therapeutic strategies.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>HIV-1 Tat is essential for viral transcription and the establishment of latency and reactivation and represents a potential target for achieving a functional cure of acquired immunodeficiency syndrome (AIDS). In this study, we identify the host E3 ubiquitin ligase TRIP12 as a positive regulator that enhances USP7-mediated K48-linked deubiquitination of Tat, thereby stabilizing Tat protein. The TRIP12-USP7-Tat regulatory axis promotes HIV-1 replication and reactivation of latent HIV-1. This work uncovers a previously unrecognized mechanism by which the host ubiquitin system regulates Tat homeostasis and highlights potential therapeutic avenues for modulating HIV-1 latency.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00396-26","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T13:00:53Z","timestamp":1778677253000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["TRIP12 promotes HIV-1 replication and latency reactivation by stabilizing Tat via USP7-mediated deubiquitination"],"prefix":"10.1128","volume":"100","author":[{"given":"Hongyun","family":"Shi","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/034haf133","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Virology and AIDS Research, Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ 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