{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:56:50Z","timestamp":1753891010410,"version":"3.41.2"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T00:00:00Z","timestamp":1670284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010058","name":"Stiftelsen L\u00e4kare mot AIDS Forskningsfond","doi-asserted-by":"publisher","award":["Fob2021-0007"],"award-info":[{"award-number":["Fob2021-0007"]}],"id":[{"id":"10.13039\/501100010058","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2016-01675, 2020-02129, 2019-00991"],"award-info":[{"award-number":["2016-01675, 2020-02129, 2019-00991"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004348","name":"Stockholms L\u00e4ns Landsting","doi-asserted-by":"publisher","award":["FoUI-955284"],"award-info":[{"award-number":["FoUI-955284"]}],"id":[{"id":"10.13039\/501100004348","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The establishment of a latency reservoir is the major obstacle for a cure of HIV-1. The shock-and-kill strategy aims to reactivate HIV-1 replication in HIV -1 latently infected cells, exposing the HIV-1-infected cells to cytotoxic lymphocytes. However, none of the latency reversal agents (LRAs) tested so far have shown the desired effect in people living with HIV-1. We observed that NK cells stimulated with a pan-caspase inhibitor induced latency reversal in co-cultures with HIV-1 latently infected cells. Synergy in HIV-1 reactivation was observed with LRAs prostratin and JQ1. The supernatants of the pan-caspase inhibitor-treated NK cells activated the HIV-1 LTR promoter, indicating that a secreted factor by NK cells was responsible for the HIV-1 reactivation. Assessing changes in the secreted cytokine profile of pan-caspase inhibitor-treated NK cells revealed increased levels of the HIV-1 suppressor chemokines MIP1\u03b1 (CCL3), MIP1\u03b2 (CCL4) and RANTES (CCL5). However, these cytokines individually or together did not induce LTR promoter activation, suggesting that CCL3-5 were not responsible for the observed HIV-1 reactivation. The cytokine profile did indicate that pan-caspase inhibitors induce NK cell activation. Altogether, our approach might be\u2013in combination with other shock-and-kill strategies or LRAs\u2013a strategy for reducing viral latency reservoirs and a step forward towards eradication of functionally active HIV-1 in infected individuals.<\/jats:p>","DOI":"10.3389\/fimmu.2022.1067767","type":"journal-article","created":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T04:32:37Z","timestamp":1670301157000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Natural killer cells induce HIV-1 latency reversal after treatment with pan-caspase inhibitors"],"prefix":"10.3389","volume":"13","author":[{"given":"Joana","family":"Furtado Mil\u00e3o","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Love","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Gourgi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas","family":"Derhaschnig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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