ORIGINAL RESEARCH article
Front. Immunol.
Sec. Viral Immunology
SMAC mimetics sensitize HIV infected cells to oncolytic virus mediated death
Provisionally accepted
- 1University of Ottawa, Department of Biochemistry, Microbiology and Immunology, Ottawa, Canada
- 2Ottawa Hospital Research Institute, Inflammation and Chronic Disease Program, Ottawa, Canada
- 3University of Toronto Leslie Dan Faculty of Pharmacy, Toronto, Canada
- 4University of Ottawa, Department of Biochemistry, Microbiology and Immunology,, Ottawa, Canada
- 5The Ottawa Hospital, Department of Medicine, Division of Infectitous Diseases, Ottawa, Canada
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Eliminating latently and persistently HIV infected cells is one of the main barriers to finding an HIV cure. We have demonstrated that cells latently/persistently infected with HIV have impaired interferon signalling, 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 killing of HIV infected cell lines and monocyte derived macrophages (MDM). We show that SMAC mimetics enhance MG1-mediate death but this is not a result of an increase in OV infection. This cell death occurs via both caspase dependent and independent mechanisms, and is not completely dependent on TNFα. Together, these results show that using SMAC mimetics alongside oncolytic viruses may be a viable strategy to eradicate latently/persistently HIV infected cells.
Keywords: HIV, SMAC mimetics, Oncolytic Viruses, MG1, VSV
Received: 14 Jul 2025; Accepted: 28 Nov 2025.
Copyright: © 2025 Molyer, Ameeriar and Angel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jonathan Angel
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