https://scholars.lib.ntu.edu.tw/handle/123456789/637363
Title: | Hepatoviruses promote very-long-chain fatty acid and sphingolipid synthesis for viral RNA replication and quasi-enveloped virus release | Authors: | Shiota, Tomoyuki Li, Zhucui GUAN-YUAN CHEN McKnight, Kevin L Shirasaki, Takayoshi Yonish, Bryan Kim, Heyjeong Fritch, Ethan J Sheahan, Timothy P Muramatsu, Masamichi Kapustina, Maryna Cameron, Craig E Li, You Zhang, Qibin Lemon, Stanley M |
Issue Date: | 20-Oct-2023 | Journal Volume: | 9 | Journal Issue: | 42 | Source: | Science advances | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/637363 | ISSN: | 2375-2548 | DOI: | 10.1126/sciadv.adj4198 |
Appears in Collections: | 醫學院附設醫院 (臺大醫院) |
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