{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:07:59Z","timestamp":1784606879523,"version":"3.55.0"},"reference-count":65,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82102387,82372247"],"award-info":[{"award-number":["82102387,82372247"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Science Foundation for Outstanding Young Scholars of Hunan Province","award":["2022JJ20033"],"award-info":[{"award-number":["2022JJ20033"]}]},{"name":"Key Project of Education Department of Hunan Province","award":["22A0035"],"award-info":[{"award-number":["22A0035"]}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82372673"],"award-info":[{"award-number":["82372673"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2024,9,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Viruses normally reprogram the host cell metabolic pathways as well as metabolic sensors to facilitate their persistence. The serine-threonine liver kinase B1 (LKB1) is a master upstream kinase of 5\u2032-AMP-activated protein kinase (AMPK) that senses the energy status and therefore regulates the intracellular metabolic homeostasis. Previous studies showed that AMPK restricts Kaposi\u2019s sarcoma-associated herpesvirus (KSHV) lytic replication in endothelial cells during primary infection and promotes primary effusion lymphoma (PEL) cell survival. However, the role of LKB1 in KSHV lytic reactivation and KSHV-associated malignancies is unclear. In this study, we found that LKB1 is phosphorylated or activated in KSHV-positive PEL cells. Mechanistically, KSHV-encoded vCyclin mediated LKB1 activation in PEL cells, as vCyclin knockout ablated, while vCyclin overexpression enhanced LKB1 activation. Furthermore, knockdown of LKB1 inactivated AMPK and induced KSHV reactivation, as indicated by the increased expression of viral lytic genes and the increased virions in supernatants. Accordingly, AMPK inhibition by functional knockdown or a pharmacologic inhibitor, Compound C, promoted KSHV reactivation in PEL cells. Furthermore, inhibition of either LKB1 or AMPK\u03b11 efficiently induced cell death by apoptosis of PEL cells both\n              <jats:italic>in vitro<\/jats:italic>\n              and\n              <jats:italic>in vivo<\/jats:italic>\n              . Together, these results identify LKB1 as a vulnerable target for PEL, which could be potentially exploited for treating other virus-associated diseases.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Kaposi\u2019s sarcoma-associated herpesvirus (KSHV) is an oncogenic virus associated with several human cancers, such as primary effusion lymphoma (PEL). Here, we showed that serine-threonine liver kinase B1 (LKB1), upstream of 5\n                <jats:italic>'<\/jats:italic>\n                AMP-activated protein kinase (AMPK), is activated by KSHV-encoded vCyclin and maintains KSHV latency in PEL cells. Inhibition of either LKB1 or AMPK enhances KSHV lytic replication from latency, which at least partially accounts for PEL cell death by apoptosis. Compound C, a potent AMPK inhibitor, induced KSHV reactivation and efficiently inhibited PEL progression\n                <jats:italic>in vivo<\/jats:italic>\n                . Thus, our work revealed that LKB1 is a potential therapeutic target for KSHV-associated cancers.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/jvi.00604-24","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T13:01:04Z","timestamp":1724850064000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["LKB1 suppresses KSHV reactivation and promotes primary effusion lymphoma progression"],"prefix":"10.1128","volume":"98","author":[{"given":"Guanya","family":"Li","sequence":"first","affiliation":[{"name":"Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University","place":["Changsha, China"]},{"name":"Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Sciences, Hunan Normal University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinan","family":"Li","sequence":"additional","affiliation":[{"name":"Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University","place":["Changsha, China"]},{"name":"Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Sciences, Hunan Normal University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Tang","sequence":"additional","affiliation":[{"name":"Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University","place":["Changsha, China"]},{"name":"Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Sciences, Hunan Normal University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University","place":["Changsha, China"]},{"name":"Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Sciences, Hunan Normal University","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shusheng","family":"Yue","sequence":"additional","affiliation":[{"name":"Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, College of Life Sciences, Hunan Normal University","place":["Changsha, China"]},{"name":"Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College 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