Editorial: Significance of Cellular Lipids for Viral Replication and Pathogenesis

Cellular lipids and their metabolism have increasingly been recognized as essential for various steps of viral replication cycles, including viral entry, genome transcription and replication, particle assembly and egress. These cellular lipids include various structural molecules, such a gangliosides, phospholipids, sterols and sphingolipids, and are localized in cellular membranes and lipid droplets (LDs). Alterations of lipid homeostasis can promote or block viral replication and are often accompanied by the production of pro-inflammatory cytokines. Therefore, cellular lipids and their metabolites are considered to be attractive targets for the development of new broadspectrum antiviral therapies. The biosynthesis of intracellular fatty acids and sterols as well as their metabolic pathways are well researched (Walther and Farese, 2012; Crawford and Desselberger, 2016). Lipid droplets (LDs) are major storage organelles of neutral lipids, such as triacylglycerols and cholesterol esters, and act as vehicles for intracellular transport (Walther et al., 2017). These organelles, and other lipids, are also important for the replication of various RNA viruses such as hepatitis C viruses, Dengue viruses (Chatel-Chaix and Bartenschlager, 2014; Bang et al., 2019), species A rotaviruses (Cheung et al., 2010), picornaviruses (Belov and vanKuppeveld, 2019; Laufman et al., 2019), noroviruses (Doerflinger et al., 2017), SARS-CoV-2 (Dias et al., 2020; Nardacci et al., 2021; Theken et al., 2021) and someDNA viruses such asMarek’s disease virus (Boodhoo et al., 2019). However, the specific mechanisms by which these viruses interact with the cellular lipidome remain incompletely understood. The roles of cellular lipids in viral replication and pathogenesis and their potential to be developed as drug targets were highlighted in seven articles in the Research Topic by Frontiers in Physiology. Avota et al. assessed the various roles played by sphingolipids during the different steps of viral replication (virus attachment and entry, viral replication, morphogenesis and budding), updating earlier reviews (Schneider-Schaulies and Schneider-Schaulies, 2015; Schneider-Schaulies et al., 2021). They also discuss the possibility to repurpose inhibitors of sphingolipid metabolism already in clinical use for treatment of viral infections. Similarly, Farfan-Morales et al. discuss the use of FDA-approved lipid-lowering drugs as host celltargeted antivirals against flavivirus disease caused by Dengue and Zika viruses. In this context the contribution by Vial et al. is of interest. In mosquitoes, which act as vectors for various human flavivirus infections, the phospholipidome is upregulated during virus replication. This finding may lead to the development of novel, host-specific antivirals with the aim to block transmission to the human host. Other researchers highlighted the potential of various lipid metabolic pathways as antiviral targets. Cellular cholesterol, as a component of cellular lipid rafts has recently gained much attention Edited and reviewed by: Nada A. Abumrad, Washington University in St. Louis, United States