2. Academic Validation
  3. Hepatoviruses promote very-long-chain fatty acid and sphingolipid synthesis for viral RNA replication and quasi-enveloped virus release

Hepatoviruses promote very-long-chain fatty acid and sphingolipid synthesis for viral RNA replication and quasi-enveloped virus release

  • Sci Adv. 2023 Oct 20;9(42):eadj4198. doi: 10.1126/sciadv.adj4198.
Tomoyuki Shiota 1,  Zhucui Li 2,  Guan-Yuan Chen 2,  Kevin L McKnight 1,  Takayoshi Shirasaki 1,  Bryan Yonish 1,  Heyjeong Kim 3,  Ethan J Fritch 3,  Timothy P Sheahan 4,  Masamichi Muramatsu 5,  Maryna Kapustina 6,  Craig E Cameron 1 3,  You Li 1 7,  Qibin Zhang 2 8,  Stanley M Lemon 1 3 7
Affiliations

Affiliations

  • 1 Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • 2 Center for Translational Biomedical Research, The University of North Carolina at Greensboro, Kannapolis, NC, USA.
  • 3 Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • 4 Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • 5 Department of Infectious Disease Research, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan.
  • 6 Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • 7 Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • 8 Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro, Greensboro, NC, USA.
PMID: 37862421 DOI: 10.1126/sciadv.adj4198
Abstract

Virus-induced changes in host lipid metabolism are an important but poorly understood aspect of viral pathogenesis. By combining nontargeted lipidomics analyses of infected cells and purified extracellular quasi-enveloped virions with high-throughput RNA sequencing and genetic depletion studies, we show that hepatitis A virus, an hepatotropic picornavirus, broadly manipulates the host cell lipid environment, enhancing synthesis of ceramides and other sphingolipids and transcriptionally activating acyl-coenzyme A synthetases and fatty acid elongases to import and activate long-chain fatty acids for entry into the fatty acid elongation cycle. Phospholipids with very-long-chain acyl tails (>C22) are essential for genome replication, whereas increases in sphingolipids support assembly and release of quasi-enveloped virions wrapped in membranes highly enriched for sphingomyelin and very-long-chain ceramides. Our data provide insight into how a pathogenic virus alters lipid flux in infected hepatocytes and demonstrate a distinction between lipid species required for viral RNA synthesis versus nonlytic quasi-enveloped virus release.

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