{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:35:03Z","timestamp":1790822103672,"version":"4.1.0"},"reference-count":80,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,10,17]],"date-time":"2023-10-17T00:00:00Z","timestamp":1697500800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["RTG 2155"],"award-info":[{"award-number":["RTG 2155"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Jena University Hospital IZKF","award":["MSP 11"],"award-info":[{"award-number":["MSP 11"]}]},{"name":"Landesgraduiertenstipendium"},{"name":"Jena University Hospital IZKF","award":["AMSP 19"],"award-info":[{"award-number":["AMSP 19"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2023,10,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Herpes simplex virus type 1 (HSV-1) is a widespread contagious pathogen, mostly causing mild symptoms on the mucosal entry side. However, systemic distribution, in particular upon reactivation of the virus in immunocompromised patients, may trigger an innate immune response and induce damage of organs. In these conditions, HSV-1 may infect vascular endothelial cells, but little is known about the regulation of HSV-1 replication and possible defense mechanisms in these cells. The current study addresses the question of whether the host cell protein AMP-activated protein kinase (AMPK), an important metabolic sensor, can control HSV-1 replication in endothelial cells. We show that downregulation of the catalytic subunits AMPK\u03b11 and\/or AMPK\u03b12 increased HSV-1 replication as monitored by TCID\n                    <jats:sub>50<\/jats:sub>\n                    titrations, while a potent AMPK agonist, MK-8722, strongly inhibited it. MK-8722 induced a persistent phosphorylation of the AMPK downstream targets acetyl-CoA carboxylase (ACC) and the rapamycin-sensitive adaptor protein of mTOR (Raptor) and, related to this, impairment of ACC1-mediated lipid synthesis and the mechanistic target of the rapamycin complex-1 (mTORC1) pathway. Since blockade of mTOR by Torin-2 as well as downregulation of ACC1 by siRNA also decreased HSV-1 replication, MK-8722 is likely to exert its anti-viral effect via mTORC1 and ACC1 inhibition. Importantly, MK-8722 was able to reduce virus replication even when added after HSV-1. Together, our data highlight the importance of endothelial cells as host cells for HSV-1 replication upon systemic infection and identify AMPK, a metabolic host cell protein, as a potential target for antiviral strategies against HSV-1 infection and its severe consequences.\n                  <\/jats:p>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Herpes simplex virus type 1 (HSV-1) is a common pathogen that causes blisters or cold sores in humans. It remains latent in infected individuals and can be reactivated multiple times. In adverse conditions, for instance, in immunocompromised patients, HSV-1 can lead to serious complications such as encephalitis, meningitis, or blindness. In these situations, infection of endothelial cells lining the surface of blood vessels may contribute to the manifestation of disease. Here, we describe the role of AMP-activated protein kinase (AMPK), a potent regulator of cellular energy metabolism, in HSV-1 replication in endothelial cells. While downregulation of AMPK potentiates HSV-1 replication, pharmacological AMPK activation inhibits it by limiting the availability of required host cell macromolecules such as proteins or fatty acids. These data highlight the role of metabolic host cell proteins as antiviral targets and reveal activation of endothelial AMPK as a potential strategy to protect from severe consequences of HSV-1 infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00417-23","type":"journal-article","created":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T09:00:26Z","timestamp":1694595626000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["AMPK protects endothelial cells against HSV-1 replication via inhibition of mTORC1 and ACC1"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8125-1413","authenticated-orcid":false,"given":"Heena","family":"Doshi","sequence":"first","affiliation":[{"name":"Institute for Molecular Cell Biology, Center for Molecular Biomedicine, Jena University Hospital","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Spengler","sequence":"additional","affiliation":[{"name":"Institute for Molecular Cell Biology, Center for Molecular Biomedicine, Jena University Hospital","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amod","family":"Godbole","sequence":"additional","affiliation":[{"name":"Institute for Molecular Cell Biology, Center for Molecular Biomedicine, Jena University Hospital","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Sing","family":"Gee","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University","place":["Parkville, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Baell","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University","place":["Parkville, Australia"]},{"name":"School of Pharmaceutical Sciences, Nanjing Tech University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan S.","family":"Oakhill","sequence":"additional","affiliation":[{"name":"Metabolic Signaling Laboratory, St. Vincent\u2019s Institute of Medical Research","place":["Fitzroy, Australia"]},{"name":"Exercise and Nutrition Research Program, Mary MacKillop Institute for Health Research, Australian Catholic University","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Henke","sequence":"additional","affiliation":[{"name":"Section of Experimental Virology, Institute of Medical Microbiology, Jena University Hospital","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1703-1925","authenticated-orcid":false,"given":"Regine","family":"Heller","sequence":"additional","affiliation":[{"name":"Institute for Molecular Cell Biology, Center for Molecular Biomedicine, Jena University Hospital","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.00733"},{"key":"e_1_3_3_3_2","unstructured":"World Health Organization . 2023. 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