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Treatment with the Caspase-1\/4 inhibitor VX-765 limited CD4<jats:sup>+<\/jats:sup> T cell loss in the spleen and reduced viral load in both the spleen and axillary LN. In situ hybridization further demonstrated a decrease in viral RNA in both the spleen and LN. Transcriptomic analysis revealed that in vivo inhibition of caspase-1\/4 led to an upregulation in host HIV restriction factors including SAMHD1 and APOBEC3A. These findings highlight the use of rFLT-3\u00a0L to augment human immune system characteristics in HIS mice to support investigations of HIV pathogenesis and test host directed therapies, though further refinements are needed to further augment LN architecture and cellular populations. The results further provide in vivo evidence of the potential to target inflammasome pathways as an avenue of host-directed therapy to limit immune dysfunction and virus replication in tissue compartments of HIV<jats:sup>+<\/jats:sup> persons.<\/jats:p>","DOI":"10.1186\/s12977-024-00641-2","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T23:02:13Z","timestamp":1714604533000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Inhibition of caspase pathways limits CD4+ T cell loss and restores host anti-retroviral function in HIV-1 infected humanized mice with augmented lymphoid tissue"],"prefix":"10.1186","volume":"21","author":[{"given":"Alex J.","family":"Holloway","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tais B.","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kubra F.","family":"Naqvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew B.","family":"Huante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuzhen","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua G.","family":"Lisinicchia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin B.","family":"Gelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice J.","family":"Endsley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Endsley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,2]]},"reference":[{"key":"641_CR1","unstructured":"HIV\/AIDS. https:\/\/www.who.int\/data\/gho\/data\/themes\/hiv-aids."},{"key":"641_CR2","doi-asserted-by":"publisher","first-page":"e1002464","DOI":"10.1371\/journal.ppat.1002464","volume":"8","author":"A Pawlowski","year":"2012","unstructured":"Pawlowski A, Jansson M, Sk\u00f6ld M, Rottenberg ME, K\u00e4llenius G. 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