{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:22:20Z","timestamp":1790356940319,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2016,2,15]],"date-time":"2016-02-15T00:00:00Z","timestamp":1455494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI093258-02"],"award-info":[{"award-number":["AI093258-02"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["AI087390-07"],"award-info":[{"award-number":["AI087390-07"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,2,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Rhesus macaque TRIM5\u03b1 (rhTRIM5\u03b1) is a retroviral restriction factor that inhibits HIV-1 infection. Previous studies have revealed that TRIM5\u03b1 restriction occurs via a two-step process. The first step is restriction factor binding, which is sufficient to inhibit infection. The second step, which is sensitive to proteasome inhibition, prevents the accumulation of reverse transcription products in the target cell. However, because of the pleotropic effects of proteasome inhibitors, the molecular mechanisms underlying the individual steps in the restriction process have remained poorly understood. In this study, we have fused the small catalytic domain of herpes simplex virus UL36 deubiquitinase (DUb) to the N-terminal RING domain of rhTRIM5\u03b1, which results in a ubiquitination-resistant protein. Cell lines stably expressing this fusion protein inhibited HIV-1 infection to the same degree as a control fusion to a catalytically inactive DUb. However, reverse transcription products were substantially increased in the DUb-TRIM5\u03b1 fusion relative to the catalytically inactive control or the wild-type (WT) TRIM5\u03b1. Similarly, expression of DUb-rhTRIM5\u03b1 resulted in the accumulation of viral cores in target cells following infection, while the catalytically inactive control and WT rhTRIM5\u03b1 induced the abortive disassembly of viral cores, indicating a role for ubiquitin conjugation in rhTRIM5\u03b1-mediated destabilization of HIV-1 cores. Finally, DUb-rhTRIM5\u03b1 failed to activate NF-\u03baB signaling pathways compared to controls, demonstrating that this ubiquitination-dependent activity is separable from the ability to restrict retroviral infection.<\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            These studies provide direct evidence that ubiquitin conjugation to rhTRIM5\u03b1-containing complexes is required for the second step of HIV-1 restriction. They also provide a novel tool by which the biological activities of TRIM family proteins might be dissected to better understand their function and underlying mechanisms of action.\n          <\/jats:p>","DOI":"10.1128\/jvi.01948-15","type":"journal-article","created":{"date-parts":[[2015,12,17]],"date-time":"2015-12-17T03:58:16Z","timestamp":1450324696000},"page":"1849-1857","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":47,"title":["TRIM5\u03b1-Mediated Ubiquitin Chain Conjugation Is Required for Inhibition of HIV-1 Reverse Transcription and Capsid Destabilization"],"prefix":"10.1128","volume":"90","author":[{"given":"Edward M.","family":"Campbell","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, 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