Glycerophospholipid remodeling is critical for orthoflavivirus infection.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
07 Oct 2024
Historique:
received: 21 02 2024
accepted: 26 09 2024
medline: 8 10 2024
pubmed: 8 10 2024
entrez: 7 10 2024
Statut: epublish

Résumé

Flavivirus infection is tightly connected to host lipid metabolism. Here, we performed shotgun lipidomics of cells infected with neurotropic Zika, West Nile, and tick-borne encephalitis virus, as well as dengue and yellow fever virus. Early in infection specific lipids accumulate, e.g., neutral lipids in Zika and some lysophospholipids in all infections. Ceramide levels increase following infection with viruses that cause a cytopathic effect. In addition, fatty acid desaturation as well as glycerophospholipid metabolism are significantly altered. Importantly, depletion of enzymes involved in phosphatidylserine metabolism as well as phosphatidylinositol biosynthesis reduce orthoflavivirus titers and cytopathic effects while inhibition of fatty acid monounsaturation only rescues from virus-induced cell death. Interestingly, interfering with ceramide synthesis has opposing effects on virus replication and cytotoxicity depending on the targeted enzyme. Thus, lipid remodeling by orthoflaviviruses includes distinct changes but also common patterns shared by several viruses that are needed for efficient infection and replication.

Identifiants

pubmed: 39375358
doi: 10.1038/s41467-024-52979-y
pii: 10.1038/s41467-024-52979-y
doi:

Substances chimiques

Glycerophospholipids 0
Ceramides 0
Phosphatidylserines 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

8683

Subventions

Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 517270163
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 517270083
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 197785619 (CRC 2021 project B10)
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 416701689
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 197785619 (CRC 2021 project Z02)

Informations de copyright

© 2024. The Author(s).

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Auteurs

Julia Hehner (J)

Institute of Virology, University of Marburg, Marburg, Germany.

Laura Schneider (L)

Institute of Virology, University of Marburg, Marburg, Germany.

Anna Woitalla (A)

Division of Bioanalytical Chemistry, Research Center Borstel - Leibniz Lung Center, Borstel, Germany.

Benjamin Ott (B)

Institute of Medical Microbiology, Justus Liebig University Giessen, Giessen, Germany.

Kim Chi Thi Vu (KCT)

Institute of Virology, University of Marburg, Marburg, Germany.

Anja Schöbel (A)

Institute of Virology, University of Marburg, Marburg, Germany.

Torsten Hain (T)

Institute of Medical Microbiology, Justus Liebig University Giessen, Giessen, Germany.

Dominik Schwudke (D)

Division of Bioanalytical Chemistry, Research Center Borstel - Leibniz Lung Center, Borstel, Germany. dschwudke@fz-borstel.de.
Thematic Translational Unit Tuberculosis, German Center for Infection Research, Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany. dschwudke@fz-borstel.de.
Airway Research Center North (ARCN), German Center for Lung Research (DZL), Site Research Center Borstel - Leibniz Lung Center, Borstel, Germany. dschwudke@fz-borstel.de.

Eva Herker (E)

Institute of Virology, University of Marburg, Marburg, Germany. eva.herker@uni-marburg.de.

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