{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:14:59Z","timestamp":1785406499401,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,9]]},"group-title":"Microbiology","reference-count":36,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01DA059538"],"award-info":[{"award-number":["R01DA059538"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01MH134402"],"award-info":[{"award-number":["R01MH134402"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R56AI157872"],"award-info":[{"award-number":["R56AI157872"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Despite of the highly potent antiretroviral therapies, HIV-1 establishes persistent infection and causes chronic inflammation in AIDS patients. Beyond CD4+ T cells, HIV-1 infects myeloid cells, including circulating monocytes and tissue-resident macrophages, and integrates with host genomes to form stable viral reservoirs. To achieve a functional HIV cure, latency-promoting agents (LPAs) have been developed for the \u201cblock-and-lock\u201d strategy to reinforce deep HIV-1 latency and permanently silence proviruses. However, most LPAs have been tested mainly in CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells, and their efficacy in myeloid cells remains unclear. In this study, we reported that levosimendan (LSM), a drug approved for clinic use to treat heart failures, is able to inhibit HIV lytic infection and reactivation in myeloid cells. LSM blocked viral lytic reactivation in HIV-1 latently infected monocytic cells (TH89GFP, U1) and microglial cells (HC69). LSM also inhibited HIV infection in human induced pluripotent stem cell (iPSC) derived microglia (iMG), primary human resident liver macrophages (Kupffer cells) as well as human monocyte-derived macrophages (MDMs). Furthermore, we demonstrated that overexpression of a predicted drug target of LSM, the conserved serine\/threonine kinase RIOK1 (RIO kinase 1), overcomes LSM\u2019s anti-HIV effect. Overall, our studies concluded that LSM is a promising LPA to inhibit HIV-1 infection in myeloid cells in the RIOK1-dependent manner.\n                <\/jats:p>","DOI":"10.64898\/2026.04.08.717218","type":"posted-content","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T05:45:14Z","timestamp":1775799914000},"source":"Crossref","is-referenced-by-count":0,"title":["Levosimendan inhibits HIV-1 infection in myeloid cells in the RIOK1-dependent manner"],"prefix":"10.64898","author":[{"given":"Jinshan","family":"He","sequence":"first","affiliation":[{"name":"Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngmin","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume N","family":"Fiches","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kateepe ASN","family":"Shanaka","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thurbu T","family":"Lepcha","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suha","family":"Eleya","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Netty G","family":"Santoso","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Zhe","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH, 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041301350548000_2026.04.08.717218v1.1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a007096"},{"key":"2026041301350548000_2026.04.08.717218v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.09.044"},{"key":"2026041301350548000_2026.04.08.717218v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4319"},{"key":"2026041301350548000_2026.04.08.717218v1.4","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-018-9809-2"},{"key":"2026041301350548000_2026.04.08.717218v1.5","doi-asserted-by":"crossref","first-page":"362","DOI":"10.3389\/fcimb.2019.00362","article-title":"Microglial Cells: The Main HIV-1 Reservoir in the Brain","volume":"9","year":"2019","journal-title":"Front Cell Infect Microbiol"},{"key":"2026041301350548000_2026.04.08.717218v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2015.5"},{"key":"2026041301350548000_2026.04.08.717218v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.02.013"},{"key":"2026041301350548000_2026.04.08.717218v1.8","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1374"},{"key":"2026041301350548000_2026.04.08.717218v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.01.014"},{"key":"2026041301350548000_2026.04.08.717218v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/nature11286"},{"key":"2026041301350548000_2026.04.08.717218v1.11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005063"},{"key":"2026041301350548000_2026.04.08.717218v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.12.003"},{"key":"2026041301350548000_2026.04.08.717218v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.09.080"},{"key":"2026041301350548000_2026.04.08.717218v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2017.08.013"},{"key":"2026041301350548000_2026.04.08.717218v1.15","doi-asserted-by":"crossref","first-page":"I2","DOI":"10.1093\/eurheartj\/suy039","article-title":"Use of levosimendan in acute heart failure","volume":"20","year":"2018","journal-title":"Eur Heart J Suppl"},{"key":"2026041301350548000_2026.04.08.717218v1.16","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1007\/s10557-018-6838-2","article-title":"Levosimendan in Acute and Advanced Heart Failure: an Expert Perspective on Posology and Therapeutic Application","volume":"32","year":"2018","journal-title":"Cardiovasc Drugs Ther"},{"key":"2026041301350548000_2026.04.08.717218v1.17","doi-asserted-by":"crossref","first-page":"e1006619","DOI":"10.1371\/journal.pcbi.1006619","article-title":"Rational discovery of dual-indication multi-target PDE\/Kinase inhibitor for precision anti-cancer therapy using structural systems pharmacology","volume":"15","year":"2019","journal-title":"PLoS Comput Biol"},{"key":"2026041301350548000_2026.04.08.717218v1.18","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-020-00544-y"},{"key":"2026041301350548000_2026.04.08.717218v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-15411-9"},{"key":"2026041301350548000_2026.04.08.717218v1.20","doi-asserted-by":"crossref","unstructured":"Ribeiro E , Vale N . 2023. Understanding the Clinical Use of Levosimendan and Perspectives on its Future in Oncology. Biomolecules 13.","DOI":"10.3390\/biom13091296"},{"key":"2026041301350548000_2026.04.08.717218v1.21","doi-asserted-by":"crossref","first-page":"6566","DOI":"10.3390\/cimb46070391","article-title":"An In Vitro Investigation of the Antiproliferative and Antimetastatic Effects of Levosimendan: Potential Drug Repurposing for Cervical Cancer","volume":"46","year":"2024","journal-title":"Curr Issues Mol Biol"},{"key":"2026041301350548000_2026.04.08.717218v1.22","doi-asserted-by":"crossref","first-page":"189100","DOI":"10.1016\/j.bbcan.2024.189100","article-title":"A role for RIO kinases in the crosshair of cancer research and therapy","volume":"1879","year":"2024","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"2026041301350548000_2026.04.08.717218v1.23","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E11-07-0639"},{"key":"2026041301350548000_2026.04.08.717218v1.24","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/s41420-023-01704-7","article-title":"The RioK1 network determines p53 activity at multiple levels","volume":"9","year":"2023","journal-title":"Cell Death Discov"},{"key":"2026041301350548000_2026.04.08.717218v1.25","doi-asserted-by":"publisher","DOI":"10.1007\/s11904-024-00692-2"},{"key":"2026041301350548000_2026.04.08.717218v1.26","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s40588-024-00234-9","article-title":"Myeloid Cell Reservoirs: Role in HIV-Host Interplay and Strategies for Myeloid Reservoir Elimination","volume":"11","year":"2024","journal-title":"Current Clinical Microbiology Reports"},{"key":"2026041301350548000_2026.04.08.717218v1.27","doi-asserted-by":"crossref","first-page":"134","DOI":"10.3389\/fcimb.2020.00134","article-title":"Measuring the Success of HIV-1 Cure Strategies","volume":"10","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"2026041301350548000_2026.04.08.717218v1.28","doi-asserted-by":"crossref","unstructured":"Moranguinho I , Valente ST . 2020. Block-And-Lock: New Horizons for a Cure for HIV-1. Viruses 12.","DOI":"10.3390\/v12121443"},{"key":"2026041301350548000_2026.04.08.717218v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.10.056"},{"key":"2026041301350548000_2026.04.08.717218v1.30","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-407395"},{"key":"2026041301350548000_2026.04.08.717218v1.31","doi-asserted-by":"crossref","unstructured":"Nasr N , Alshehri AA , Wright TK , Shahid M , Heiner BM , Harman AN , Botting RA , Helbig KJ , Beard MR , Suzuki K , Kelleher AD , Hertzog P , Cunningham AL . 2017. Mechanism of Interferon-Stimulated Gene Induction in HIV-1-Infected Macrophages. J Virol 91.","DOI":"10.1128\/JVI.00744-17"},{"key":"2026041301350548000_2026.04.08.717218v1.32","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1160\/TH14-06-0549","article-title":"Levosimendan exerts anti-inflammatory effects on cardiac myocytes and endothelial cells in vitro","volume":"113","year":"2015","journal-title":"Thromb Haemost"},{"key":"2026041301350548000_2026.04.08.717218v1.33","doi-asserted-by":"crossref","first-page":"13398","DOI":"10.1038\/s41598-019-48792-z","article-title":"Levosimendan pretreatment improves survival of septic rats after partial hepatectomy and suppresses iNOS induction in cytokine-stimulated hepatocytes","volume":"9","year":"2019","journal-title":"Sci Rep"},{"key":"2026041301350548000_2026.04.08.717218v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2005.07.037"},{"key":"2026041301350548000_2026.04.08.717218v1.35","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s11010-016-2892-x","article-title":"Benzimidazole inhibitors of protein kinase CK2 potently inhibit the activity of atypical protein kinase Rio1","volume":"426","year":"2017","journal-title":"Mol Cell Biochem"},{"key":"2026041301350548000_2026.04.08.717218v1.36","doi-asserted-by":"crossref","first-page":"5745","DOI":"10.7150\/jca.60596","article-title":"Co-overexpression of RIOK1 and AKT1 as a prognostic risk factor in glioma","volume":"12","year":"2021","journal-title":"J Cancer"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.08.717218","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T08:35:18Z","timestamp":1776069318000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.04.08.717218"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,9]]},"references-count":36,"URL":"https:\/\/doi.org\/10.64898\/2026.04.08.717218","relation":{},"subject":[],"published":{"date-parts":[[2026,4,9]]},"subtype":"preprint"}}