key: cord-0834491-h14sawxe authors: Desselberger, Ulrich; Pohl, Carolina Henritta; O’Neill, Hester Gertruida title: Editorial: Significance of Cellular Lipids for Viral Replication and Pathogenesis date: 2022-04-28 journal: Front Physiol DOI: 10.3389/fphys.2022.906205 sha: 00b0d9ad00365abe6672fe62b3db19af5b45f7e3 doc_id: 834491 cord_uid: h14sawxe nan as being required for cellular entry of many enveloped and nonenveloped viruses (Ripa et al., 2021; Sanders et al., 2021) . In the review by Glitscher and Hildt, the fact that viruses redistribute cellular cholesterol during infection was emphasised. Furthermore, it was proposed that strategies to manage the distribution of cellular cholesterol during viral infection, rather than a global reduction of cholesterol metabolism, be investigated for the development of broad-spectrum antivirals. Measles virus replication in primary human lymphocytes was found to be significantly reduced by inhibitors of ceramidase and sphingosine kinases 1 and 2 (Chithelen et al.), which correlated with the blockage of the phosphorylation of cellular translation factors. Lipid droplets are important for rotavirus replication and take part in the formation of viral factories, termed viroplasms (Cheung et al., 2010) . Crawford et al. reported that a recombinant rotavirus A strain containing a mutant NSP2 protein exhibits delayed viroplasm formation. They observed an early interaction of NSP2 with phosphorylated perilipin 1 located on LDs, thus dissecting part of the molecular mechanism of viroplasm-LD interaction during rotavirus replication. Following rotavirus infection, Sander et al. observed an increase in the production of the arachidonic acid metabolite, the eicosanoid prostaglandin E 2 . This metabolite has been implicated in various steps of viral replication, including viral binding to cellular receptors, viral gene expression, increase in pro-inflammatory cytokines and the production and release of nascent virions (Sander et al., 2017) . In the current study, co-localization between prostaglandin E 2 and viroplasms was shown. Inhibitors of prostaglandin E 2 synthesis, such as indomethacin, reduced the yield of infectious viral progeny by approximately 1 log step. This finding points to a role of prostaglandin E 2 in enhancement of rotavirus attachment and internalisation. Viral factories have recently been recognized as liquid-liquid phase separation (LLPS)-driven protein-RNA condensates (Etibor et al., 2021; Geiger et al., 2021; Papa et al., 2021) which change their material properties over time and can interact with LDs at later stages of infection. Details of the interaction of the biomolecular condensates with cellular compounds (LDs, tubulin, and others) remain to be elucidated. Up to now, the interaction of the cellular lipidome with replication steps of mammalian viruses has been explored mainly in vitro. Translational research of these relationships in intestinal organoids (Saxena et al., 2015; Ettayebi et al., 2016) and suitable animal models is very much at the beginning but is promising for the development of broad-spectrum antiviral therapy. However, this pathway may not always be straightforward. In the search of licensed drugs for repurposing to treat COVID-19 disease, it was recently found that most of the drugs with antiviral activity were cationic amphiphilic compounds associated with the development of phospholipidosis in cells and organs, thus confounding this avenue of drug discovery (Tummino et al., 2021) . While interference with lipid metabolism may hold the potential for the development of broad-spectrum antiviral therapies, this is a complex approach which will require further in-depth basic research. UD prepared the first draft; CP and HO reviewed and edited. All authors approved the final submitted version. 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