{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T03:02:09Z","timestamp":1760151729482,"version":"build-2065373602"},"reference-count":60,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,12]],"date-time":"2022-09-12T00:00:00Z","timestamp":1662940800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG)","doi-asserted-by":"publisher","award":["324484564"],"award-info":[{"award-number":["324484564"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Arenaviruses include important zoonotic pathogens that cause hemorrhagic fever (e.g., Jun\u00edn virus; JUNV) as well as other viruses that are closely related but apathogenic (e.g., Tacaribe virus; TCRV). We have found that, while TCRV and JUNV differ in their ability to induce apoptosis in infected cells, due to active inhibition of caspase activation by the JUNV nucleoprotein, both viruses trigger similar upstream pro-apoptotic signaling events, including the activation\/phosphorylation of p53. In the case of TCRV, the pro-apoptotic factor Bad is also phosphorylated (leading to its inactivation). These events clearly implicate upstream kinases in regulating the induction of apoptosis. Consistent with this, here we show activation in TCRV-infected cells of the stress-activated protein kinases p38 and JNK, which are known to regulate p53 activation, as well as the downstream kinase MK2 and transcription factor c-Jun. We also observed the early transient activation of Akt, but not Erk. Importantly, the chemical inhibition of Akt, p38, JNK and c-Jun all dramatically reduced viral growth, even though we have shown that inhibition of apoptosis itself does not. This indicates that kinase activation is crucial for viral infection, independent of its downstream role in apoptosis regulation, a finding that has the potential to shed further light on the determinants of arenavirus pathogenesis, as well as to inform future therapeutic approaches.<\/jats:p>","DOI":"10.3390\/v14092018","type":"journal-article","created":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:15:02Z","timestamp":1663114502000},"page":"2018","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Regulation of Stress-Activated Kinases in Response to Tacaribe Virus Infection and Its Implications for Viral Replication"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-8337","authenticated-orcid":false,"given":"Julia","family":"Holzerland","sequence":"first","affiliation":[{"name":"Laboratory for Arenavirus Biology, Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucie","family":"F\u00e9n\u00e9ant","sequence":"additional","affiliation":[{"name":"Laboratory for Arenavirus Biology, Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9528-5130","authenticated-orcid":false,"given":"Allison","family":"Groseth","sequence":"additional","affiliation":[{"name":"Laboratory for Arenavirus Biology, Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1099\/jgv.0.001280","article-title":"ICTV Virus Taxonomy Profile: Arenaviridae","volume":"100","author":"Radoshitzky","year":"2019","journal-title":"J. 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