ABSTRACT
Lipid droplets (LDs) are organelles involved in lipid storage, maintenance of energy homeostasis, protein sequestration, signaling events and inter-organelle interactions. Recently, LDs have been shown to favor the replication of members from different viral families, such as the Flaviviridae and Coronaviridae. In this work, we show that LDs are essential organelles for members of the Arenaviridae family. A virus-driven reduction of LD number was observed in cultures infected with Junín mammarenavirus (JUNV), caused in part by action of the viral nucleoprotein. Notably, we identified a new pool of nucleoprotein and viral RNA that localizes in the vicinity of LDs, suggesting that LDs play a role during the viral replication cycle. Regarding the mechanism behind LD exhaustion, we found evidence that lipophagy is involved in LD degradation with the resulting fatty acids being substrates of fatty acid β-oxidation, which fuels viral multiplication. This work highlights the importance of LDs during the replication cycle of JUNV, contributing to the knowledge of the metabolic changes these mammarenaviruses cause in their hosts.
Footnotes
Author contributions
Conceptualization: C.A.V., C.C.G., S.M.C.; Methodology: C.A.V., J.M.H., K.E.L., J.P.M., M.A.C.C.; Formal analysis: C.A.V., C.C.G., S.M.C.; Investigation: C.A.V., B.E.-P.; Resources: A.G., M.O., L.O., C.M.-F.; Writing - original draft: S.M.C.; Writing - review & editing: C.A.V., B.E.-P., J.M.H., A.G., M.O., L.O., C.M.-F., C.C.G., S.M.C.; Visualization: C.A.V.; Supervision: C.C.G., S.M.C.; Funding acquisition: C.C.G., S.M.C.
Funding
This work was funded by the Universidad de Buenos Aires under grant UBACyT 2020-2022 (S.C.); by Agencia Nacional de Promoción Científica y Tecnológica under grants PICT-2021-0138 (S.C.) and PICT-2021-1316 (C.G.) and by Consejo Nacional de Investigaciones Científicas y Técnicas under grant PIP 11220210100168CO (C.G.). L.O. received funding from the Leibniz Association, grant no. J59/18. A.G. received intramural funding by the Friedrich-Loeffler-Institut. The collaboration with C.M.-F. laboratory in Germany was supported by a The Company of Biologists travel grant and an ISAR Chu Family Foundation Scholarships for Early Career Women in Science. The collaboration with M.O. laboratory in USA was supported by the Fulbright Commission under a Fulbright-Ministry of Education scholarship.
Data availability
All relevant data can be found within the article and its supplementary information.