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While reduced MHC-I expression would be expected to support targeting by NK cells, a subpopulation of infected CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells consistently resists multiple rounds of NK cell natural and antibody-dependent cytotoxicity. Studies further reveal that the HIV accessory protein Vpr induces expression of\n                  <jats:italic>TNFRSF10B<\/jats:italic>\n                  (TRAIL-R2) in CD4\n                  <jats:sup>+<\/jats:sup>\n                  T cells, with \u2018survivors\u2019 of NK cell targeting exhibiting relatively higher MHC-I and weaker expression of TRAIL-R2. In fact, reverse TRAIL signaling in NK cells leads to the release of perforin and granzymes, a pathway limited when TRAIL-R2 expression is diminished. Thus, independent of canonical death receptor signaling, TRAIL-R2 serves as an activating ligand that augments NK cell killing. These observations demonstrate that through Vpr, HIV can regulate the TRAIL\/TRAIL-R2 axis to control NK cell functionality.\n                <\/jats:p>","DOI":"10.64898\/2026.04.15.718741","type":"posted-content","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T04:00:17Z","timestamp":1776657617000},"source":"Crossref","is-referenced-by-count":1,"title":["Loss of Vpr-driven TRAIL-R2 expression protects HIV-infected cells from non-canonical NK cell TRAIL attack"],"prefix":"10.64898","author":[{"given":"Paula E","family":"Grasberger","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Massachusetts Chan Medical School, Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail R","family":"Sondrini","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Massachusetts Chan Medical School, Worcester, MA 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