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

Autor: Shiota T; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Li Z; Center for Translational Biomedical Research, The University of North Carolina at Greensboro, Kannapolis, NC, USA., Chen GY; Center for Translational Biomedical Research, The University of North Carolina at Greensboro, Kannapolis, NC, USA., McKnight KL; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Shirasaki T; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Yonish B; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Kim H; Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Fritch EJ; Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Sheahan TP; Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Muramatsu M; Department of Infectious Disease Research, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Hyogo, Japan., Kapustina M; Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Cameron CE; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Li Y; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Zhang Q; Center for Translational Biomedical Research, The University of North Carolina at Greensboro, Kannapolis, NC, USA.; Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro, Greensboro, NC, USA., Lemon SM; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2023 Oct 20; Vol. 9 (42), pp. eadj4198. Date of Electronic Publication: 2023 Oct 20.
DOI: 10.1126/sciadv.adj4198
Abstrakt: 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.
Databáze: MEDLINE