Intracellular lipid droplet accumulation occurs early following viral infection and is required for an efficient interferon response.

Autor: Monson EA; Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, VIC, Australia., Crosse KM; Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, VIC, Australia., Duan M; La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia., Chen W; La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia., O'Shea RD; Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, VIC, Australia., Wakim LM; Department of Microbiology and Immunology, University of Melbourne, at Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia., Carr JM; Microbiology and Infectious Diseases, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia., Whelan DR; La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia., Helbig KJ; Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, VIC, Australia. k.helbig@latrobe.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Jul 14; Vol. 12 (1), pp. 4303. Date of Electronic Publication: 2021 Jul 14.
DOI: 10.1038/s41467-021-24632-5
Abstrakt: Lipid droplets (LDs) are increasingly recognized as critical organelles in signalling events, transient protein sequestration and inter-organelle interactions. However, the role LDs play in antiviral innate immune pathways remains unknown. Here we demonstrate that induction of LDs occurs as early as 2 h post-viral infection, is transient and returns to basal levels by 72 h. This phenomenon occurs following viral infections, both in vitro and in vivo. Virally driven in vitro LD induction is type-I interferon (IFN) independent, and dependent on Epidermal Growth Factor Receptor (EGFR) engagement, offering an alternate mechanism of LD induction in comparison to our traditional understanding of their biogenesis. Additionally, LD induction corresponds with enhanced cellular type-I and -III IFN production in infected cells, with enhanced LD accumulation decreasing viral replication of both Herpes Simplex virus 1 (HSV-1) and Zika virus (ZIKV). Here, we demonstrate, that LDs play vital roles in facilitating the magnitude of the early antiviral immune response specifically through the enhanced modulation of IFN following viral infection, and control of viral replication. By identifying LDs as a critical signalling organelle, this data represents a paradigm shift in our understanding of the molecular mechanisms which coordinate an effective antiviral response.
(© 2021. The Author(s).)
Databáze: MEDLINE
Externí odkaz: