{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:01:45Z","timestamp":1785402105824,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,3]]},"group-title":"Microbiology","reference-count":84,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH","award":["R21 AI145650"],"award-info":[{"award-number":["R21 AI145650"]}]},{"name":"NIH","award":["P51 OD011132"],"award-info":[{"award-number":["P51 OD011132"]}]},{"name":"NIH","award":["P30 AI050409"],"award-info":[{"award-number":["P30 AI050409"]}]},{"name":"NIH","award":["S10OD026799"],"award-info":[{"award-number":["S10OD026799"]}]},{"award":["University Research Committee award"],"award-info":[{"award-number":["University Research Committee award"]}],"id":[{"id":"https:\/\/ror.org\/03czfpz43","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>The establishment of a reservoir of latently infected CD4+ T cells that persist on antiretroviral therapy (ART) through proliferation represents the main barrier to HIV cure. Here, we evaluated in macaques a therapeutic approach targeting Wnt and Notch pathways that regulate T cell proliferation and differentiation during acute SIV infection, when the viral reservoir is seeded. The combination of PRI-724 and LY3039478 led to reprogramming of central memory CD4+ T cells away from quiescence and stemness toward a metabolically active effector profile resulting in reduced infection of central memory CD4+ T cells. Following sustained ART, levels of SIV RNA in CD4+ T cells were higher in the PRI-724 + LY3039478-treated group compared to controls, although SIV DNA was similar. These findings suggest that stemness pathway inhibition promotes memory T cell differentiation leading to a more transcriptionally active reservoir and has potential to synergize with \u201cshock-and-kill\u201d approaches to reduce HIV persistence.<\/jats:p>","DOI":"10.64898\/2026.07.02.734630","type":"posted-content","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T15:30:18Z","timestamp":1783092618000},"source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of Stemness Pathways during Acute SIV Limits Infection of Central Memory CD4+ T Cells and Alters Viral Reservoir Activity in Macaques"],"prefix":"10.64898","author":[{"given":"Riri Rizkianty","family":"Hamid","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Ruiz-Salinas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Emory 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