{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T13:25:58Z","timestamp":1774099558067,"version":"3.50.1"},"reference-count":71,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI141495, R61AI169659, R21AI170070, R21AI181742, P30CA086862-24S1"],"award-info":[{"award-number":["R01AI141495, R61AI169659, R21AI170070, R21AI181742, P30CA086862-24S1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,7,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Sterile alpha motif (SAM) and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) inhibits HIV-1 replication in non-dividing cells by reducing the intracellular dNTP pool. While SAMHD1 is known to promote spontaneous apoptosis, its role in HIV-1-induced apoptosis and the underlying mechanisms remain unclear. In this study, we identify a novel mechanism by which SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells via the mitochondrial pathway. We demonstrate that SAMHD1 enhances apoptosis induced by HIV-1 infection in dividing monocytic THP-1 and U937 cell lines, but not in differentiated macrophage-like cells. Mechanistically, SAMHD1 expression reduces mitochondrial membrane potential and promotes cytochrome c release in HIV-1-infected THP-1 cells, thereby augmenting the mitochondrial apoptotic pathway. Furthermore, SAMHD1-enhanced apoptosis is linked to elevated levels of the pro-apoptotic protein BCL-2-interacting killer (BIK) in cells, which contributes to enhanced apoptosis during HIV-1 infection. These findings reveal a previously unrecognized regulatory role of SAMHD1 in amplifying HIV-1-induced apoptosis in monocytic cells, highlighting its involvement in the mitochondrial apoptotic pathway.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Sterile alpha motif (SAM) and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1), a dNTP triphosphohydrolase, lowers intracellular dNTP levels and restricts HIV-1 replication in non-dividing cells. HIV-1 infection induces cell death mainly through apoptosis. While we have shown that endogenous SAMHD1 enhances spontaneous apoptosis in monocytic cells, its role in HIV-1-induced apoptosis and the underlying mechanisms remain unknown. In this study, we aim to bridge this knowledge gap by investigating the functional significance of SAMHD1 in regulating apoptosis during HIV-1 infection of immune cells. Our findings reveal a novel mechanism whereby SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells through the mitochondrial pathway. This suggests a previously unrecognized role of SAMHD1 in modulating cellular responses to HIV-1 infection.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.00425-25","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T09:01:14Z","timestamp":1748422874000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells via the mitochondrial pathway"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7248-9410","authenticated-orcid":false,"given":"Hua","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Carver College of Medicine, The University of Iowa","place":["Iowa City, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3682-7571","authenticated-orcid":false,"given":"Pak-Hin Hinson","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Carver College of Medicine, The University of Iowa","place":["Iowa City, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5468-2487","authenticated-orcid":true,"given":"Li","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Carver College of Medicine, The University of Iowa","place":["Iowa City, 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