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We engineered an isogenic Tat-deficient derivative of the HIVGKO dual-reporter virus that preserves native proviral architecture, enabling longitudinal measurements across diverse integration sites in primary CD4\u207a T cells and Jurkat cells. Across thousands of proviruses, host factors alone supported a restricted baseline, with Tat-null proviruses producing \u223c4%\u201315% of wild-type protein output and remaining constrained under strong stimulation. Chromatin immunoprecipitation-seq profiling revealed that Tat is dispensable for promoter-proximal RNAPII engagement and pausing but required for efficient CDK9 recruitment, Ser2 phosphorylation, and productive elongation, defining a ceiling for Tat-independent transcription. Tat deficiency reduced overall RNAPII occupancy without increased promoter-proximal accumulation. Genome-wide mapping using Tat-null controls revealed broad Tat association with active host loci and modest increases in elongation-factor occupancy; however, host-gene RNA gains were small (\u223c1.05\u20131.49\u00d7) and poorly correlated with Tat binding. Instead, elongation-associated chromatin features better predicted responsiveness. Together, these findings define a framework separating host-driven transcription from Tat-dependent scaling and explain Tat\u2019s disproportionate potency at the provirus.<\/jats:p>","DOI":"10.1093\/nar\/gkag631","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T11:51:09Z","timestamp":1781092269000},"source":"Crossref","is-referenced-by-count":0,"title":["Quantitative limits of host-driven HIV transcription and host gene control by the viral transactivator Tat"],"prefix":"10.1093","volume":"54","author":[{"given":"Chuan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology , Jupiter, FL 33458 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology , Jupiter, FL 33458 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology , Jupiter, FL 33458 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiming","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology , Jupiter, FL 33458 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7854-7554","authenticated-orcid":false,"given":"Susana T","family":"Valente","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Herbert 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