Integrated lipidomic and proteomic profiling reveals metabolic network disruption by SARS-CoV-2 variants

The rapid evolution of SARS-CoV-2 has produced myriad viral strains with increasing transmissibility and capacity for immune evasion. While effective vaccination campaigns have reduced the fatalities associated with SARS-CoV-2, infections continue, and a detailed understanding of how this virus mani...

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Bibliographic Details
Published in:Journal of lipid research Vol. 66; no. 8; p. 100860
Main Authors: Farley, Scotland E., Kyle, Jennifer E., Jahn, Helene, Bramer, Lisa M., Piehowski, Paul D., Shepmoes, Athena A., Kaiser, Brooke LD, Williams, Sarai M., Eder, Josie G., Schultz, Carsten, Tafesse, Fikadu G.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01.08.2025
Elsevier BV
American Society for Biochemistry and Molecular Biology
Elsevier
Subjects:
A549 Cells
ceramides
coronavirus
COVID-19 - metabolism
COVID-19 - virology
host-virus interaction
Humans
Lipid Metabolism
Lipidomics
Metabolic Networks and Pathways
neutral lipids
Proteome - metabolism
Proteomics
SARS-CoV-2
SARS-CoV-2 - metabolism
SARS-CoV-2 - physiology
SARS-CoV-2 variants
sphingolipids
proteomics
sphingolipids
DTT
lipid metabolism
SARS-CoV-2 variants
HCD
coronavirus
host-virus interaction
DAG
LIPA
ceramides
AACS
FADS3
SARS-CoV-2
FASN
SPT
TAG
lipidomics
neutral lipids
ISSN:0022-2275, 1539-7262, 1539-7262
Online Access:Get full text
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Summary:The rapid evolution of SARS-CoV-2 has produced myriad viral strains with increasing transmissibility and capacity for immune evasion. While effective vaccination campaigns have reduced the fatalities associated with SARS-CoV-2, infections continue, and a detailed understanding of how this virus manipulates host biochemical pathways remains elusive. We asked both whether the patterns of host lipid rewiring remained consistent across variants and whether the changes in the abundance of lipid classes are related to changes in the expression of the enzymes involved in their biosynthesis. We compared global nontargeted lipidomics on A549-ACE2 cells infected with the delta variant (B.1.617.2), or the omicron (B.1.1.529) variant to our previous results of global nontargeted lipidomics on A549-ACE2 cells infected with the original WA1 strain and further performed quantitative proteomics to assess changes in the host proteome. We found that metabolic rewiring, both on the lipid and the enzymatic level, is remarkably consistent across all three variants. We further mapped changes in the expression of host metabolic enzymes, linking enzyme expression to alterations in the abundance of specific lipids during infection. This analysis identified key proteins related to virus-mediated changes in lipid abundance, including fatty acid synthase (FASN), lysosomal acid lipase (LIPA), and ORMDL, a regulator of sphingolipid biosynthesis. These integrated lipidomic and proteomic experiments shed light on the importance of the complex network of host metabolism networks that support SARS-CoV-2 infection and suggest that lipid metabolism may be a promising avenue for uncovering conserved therapeutic targets.
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USDOE
National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID)
AC05-76RL01830
PNNL-SA--212768
ISSN:0022-2275
1539-7262
1539-7262
DOI:10.1016/j.jlr.2025.100860