Lipid Droplets: Formation, Degradation, and Their Role in Cellular Responses to Flavivirus Infections

• Published in: Microorganisms (Basel) Vol. 12; no. 4; p. 647
• Main Authors: Hsia, James Z, Liu, Dongxiao, Haynes, LaPrecious, Cruz-Cosme, Ruth, Tang, Qiyi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.04.2024
• Subjects: antiviral; Antiviral agents; Biosynthesis; CD36 antigen; Cell interaction; Cholesterol; Cytoplasm; Dengue fever; dengue virus; Dosage and administration; Droplets; Encephalitis; Endoplasmic reticulum; Fatty acid-binding protein; Fatty acids; flaviviruses; Glycerol; Glycolysis; Health aspects; Hepatitis; Homeostasis; lipid droplet; Lipids; Metabolism; Nutrients; Organelles; orthoflaviviruses; Pathogenesis; Proteins; Replication; Tropical diseases; Viral infections; Viruses; West Nile virus; Zika virus; United States; lipid droplet; lipid droplet biogenesis; lipophagy; antiviral; dengue virus; fatty acid; hepatitis C virus; Zika virus; flaviviruses; orthoflaviviruses; endoplasmic reticulum; lipid droplet contact
• ISSN: 2076-2607; 2076-2607
• DOI: 10.3390/microorganisms12040647

Lipid droplets (LDs) are cellular organelles derived from the endoplasmic reticulum (ER), serving as lipid storage sites crucial for maintaining cellular lipid homeostasis. Recent attention has been drawn to their roles in viral replication and their interactions with viruses. However, the precise biological functions of LDs in viral replication and pathogenesis remain incompletely understood. To elucidate the interaction between LDs and viruses, it is imperative to comprehend the biogenesis of LDs and their dynamic interactions with other organelles. In this review, we explore the intricate pathways involved in LD biogenies within the cytoplasm, encompassing the uptake of fatty acid from nutrients facilitated by CD36-mediated membranous protein (FABP/FATP)-FA complexes, and FA synthesis via glycolysis in the cytoplasm and the TCL cycle in mitochondria. While LD biogenesis primarily occurs in the ER, matured LDs are intricately linked to multiple organelles. Viral infections can lead to diverse consequences in terms of LD status within cells post-infection, potentially involving the breakdown of LDs through the activation of lipophagy. However, the exact mechanisms underlying LD destruction or accumulation by viruses remain elusive. The significance of LDs in viral replication renders them effective targets for developing broad-spectrum antivirals. Moreover, considering that reducing neutral lipids in LDs is a strategy for anti-obesity treatment, LD depletion may not pose harm to cells. This presents LDs as promising antiviral targets for developing therapeutics that are minimally or non-toxic to the host.