{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:46:26Z","timestamp":1766040386454,"version":"3.48.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Elimination of latently and persistently HIV-infected cells is one of the main barriers to finding a cure for HIV. We have demonstrated that cells latently\/persistently infected with HIV impair interferon signaling, which makes them susceptible to selective infection and killing by the oncolytic virus (OV) MG1. Sensitizing these cells to MG1-mediated killing can be expected to make MG1 a more effective therapeutic. As small-molecule second mitochondria-derived activator of caspases (SMAC) mimetics have been shown to increase OV-mediated death in cancer models, we used the SMAC mimetics LCL-161 and birinapant alongside MG1 to enhance the killing of HIV-infected cell lines and monocyte-derived macrophages (MDMs). We show that SMAC mimetics enhance MG1-mediated death, but that this is not a result of an increase in OV infection. This cell death occurs via both caspase-dependent and caspase-independent mechanisms and is not completely dependent on tumor necrosis factor alpha (TNF\u03b1). Together, these results show that the use of SMAC mimetics alongside OVs may be a viable strategy to eradicate latently\/persistently HIV-infected cells.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1665811","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T06:43:25Z","timestamp":1766040205000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["SMAC mimetics sensitize HIV-infected cells to oncolytic virus-mediated death"],"prefix":"10.3389","volume":"16","author":[{"given":"Bengisu","family":"Molyer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmeen","family":"Ameeriar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan 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