{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T13:10:35Z","timestamp":1779369035665,"version":"3.53.0"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The shock\u2010and\u2010kill strategy aims to eliminate the human immunodeficiency virus type 1 (HIV\u20101) reservoir by reactivating latent virus with latency\u2010reversing agents, thereby making infected cells visible for immune\u2010mediated clearance. Despite promising in vitro and\n                    <jats:italic>ex vivo<\/jats:italic>\n                    results, clinical trials have shown limited success, likely due to the heterogeneity and inefficient elimination of reactivated cells by immune effectors such as natural killer (NK) cells. One barrier to NK cell function is the inhibitory NKG2A\u2013HLA\u2010E interaction, which dampens antiviral responses. Proteasome inhibition has been shown in cancer models to downregulate HLA\u2010E and enhance NK\u2010cell cytotoxicity, but its effect on HIV\u20101 latency remains unexplored. In this study, we demonstrate that proteasome inhibition not only reverses latency in HIV\u20101\u2010infected cell lines and primary CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells but also reduces HLA\u2010E expression. Additionally, proteasome inhibition lowered NKGA levels on NK cells, further enhancing their cytotoxic capacity. Together, these findings suggest that proteasome inhibition could simultaneously boost both phases of the shock\u2010and\u2010kill strategy, by reactivating latent HIV\u20101 and by improving NK cell\u2010mediated clearance through disruption of the NKG2A\u2013HLA\u2010E axis. This dual effect may significantly strengthen the \u201ckill\u201d phase of the shock\u2010and\u2010kill approach and could represent a promising path toward achieving a functional HIV\u20101 cure.\n                  <\/jats:p>","DOI":"10.1002\/jmv.70895","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:26:37Z","timestamp":1774531597000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteasome Inhibition Reactivates Latent HIV\u20101 and Boosts NK Cell Killing via HLA\u2010E Downregulation"],"prefix":"10.1002","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0703-5663","authenticated-orcid":false,"given":"Thessa","family":"Laeremans","sequence":"first","affiliation":[{"name":"Neuro\u2010Aging and Viro\u2010Immunotherapy Research Group Vrije Universiteit Brussel Brussels 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