{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T17:56:45Z","timestamp":1770919005613,"version":"3.50.1"},"reference-count":57,"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:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"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":[{"name":"German Research Foundation DFG","award":["CRC1021 subproject A02"],"award-info":[{"award-number":["CRC1021 subproject A02"]}]},{"DOI":"10.13039\/100010127","name":"J\u00fcrgen-Manchot-Stiftung","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010127","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>Little is known regarding the molecular mechanisms that highly pathogenic Marburg virus (MARV) utilizes to transcribe and replicate its genome. Previous studies assumed that dephosphorylation of the filoviral transcription factor VP30 supports transcription, while phosphorylated VP30 reduces transcription. Here, we focused on the role of the host protein phosphatase 2A (PP2A) for VP30 dephosphorylation and promotion of viral transcription. We could show that MARV NP interacts with the subunit B56 of PP2A, as previously shown for the Ebola virus, and that this interaction is important for MARV transcription activity. Inhibition of the interaction between PP2A and NP either by mutating the B56 binding motif encoded on NP, or the use of a PP2A inhibitor, induced VP30 hyperphosphorylation, and as a consequence a decrease of MARV transcription as well as viral growth. These results suggest that NP plays a key role in the dephosphorylation of VP30 by recruiting PP2A. Generation of recombinant (rec) MARV lacking the PP2A-B56 interaction motif on NP was not possible suggesting an essential role of PP2A-mediated VP30 dephosphorylation for the MARV replication cycle. Likewise, we were not able to generate recMARV containing VP30 phosphomimetic mutants indicating that dynamic cycles of VP30 de- and rephosphorylation are a prerequisite for an efficient viral life cycle. As the specific binding motifs of PP2A-B56 and VP30 within NP are highly conserved among the filoviral family, our data suggest a conserved mechanism for filovirus VP30 dephosphorylation by PP2A, revealing the host factor PP2A as a promising target for pan-filoviral therapies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>Our study elucidates the crucial role of host protein phosphatase 2A (PP2A) in Marburg virus (MARV) transcription. The regulatory subunit B56 of PP2A facilitates VP30 dephosphorylation, and hence transcription activation, via binding to NP. Our results, together with previous data, reveal a conserved mechanism of filovirus VP30 dephosphorylation by host factor PP2A at the NP interface and provide novel insights into potential pan-filovirus therapies.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jvi.01047-24","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":5,"title":["The cellular protein phosphatase 2A is a crucial host factor for Marburg virus transcription"],"prefix":"10.1128","volume":"98","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0056-7065","authenticated-orcid":false,"given":"Isabel","family":"von Creytz","sequence":"first","affiliation":[{"name":"Institute of Virology, Philipps-University Marburg","place":["Marburg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelius","family":"Rohde","sequence":"additional","affiliation":[{"name":"Institute of Virology, Philipps-University Marburg","place":["Marburg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6061-8019","authenticated-orcid":true,"given":"Nadine","family":"Biedenkopf","sequence":"additional","affiliation":[{"name":"Institute of Virology, Philipps-University Marburg","place":["Marburg, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1159\/000149300"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-023-05834-2"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00069-06"},{"key":"e_1_3_4_5_2","first-page":"39","article-title":"Ebola haemorrhagic fever virus: pathogenesis, immune responses, potential prevention","volume":"54","author":"Marcinkiewicz J","year":"2014","unstructured":"Marcinkiewicz J, Bryniarski K, Nazimek K. 2014. 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