A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants, 2022, Farley et al.

[SNT Gatchaman]

A global lipid map reveals host dependency factors conserved across SARS-CoV-2 variants
Farley, Scotland E.; Kyle, Jennifer E.; Leier, Hans C.; Bramer, Lisa M.; Weinstein, Jules B.; Bates, Timothy A.; Lee, Joon-Yong; Metz, Thomas O.; Schultz, Carsten; Tafesse, Fikadu G.

A comprehensive understanding of host dependency factors for SARS-CoV-2 remains elusive. Here, we map alterations in host lipids following SARS-CoV-2 infection using nontargeted lipidomics.

We find that SARS-CoV-2 rewires host lipid metabolism, significantly altering hundreds of lipid species to effectively establish infection. We correlate these changes with viral protein activity by transfecting human cells with each viral protein and performing lipidomics. We find that lipid droplet plasticity is a key feature of infection and that viral propagation can be blocked by small-molecule glycerolipid biosynthesis inhibitors. We find that this inhibition was effective against the main variants of concern (alpha, beta, gamma, and delta), indicating that glycerolipid biosynthesis is a conserved host dependency factor that supports this evolving virus.

Link | PDF (Nature Communications)

 

[SNT Gatchaman]

We show that host cells undergo profound lipid remodeling after infection with SARS-CoV-2, and that many distinctive features of infection are conserved in infection across multiple cell types. We show that lipid droplet proliferation is a consequence of infection, and that both TAG synthesis and lipolysis are required for effective replication. The lipid droplet phenotype appears to be part of a profound reprogramming of cellular lipid metabolism which is induced directly by individual viral proteins.

We find that many additional lipid species and families change upon infection, the investigation of which is far beyond the scope of this paper. Notably, ceramide increases (especially dramatically in A549-ACE2 cells), in agreement with previous observations in Vero E6 cells, a lipid with profound structural and signaling roles.

 

[Ash]

Oh man.