Japanese Encephalitis Virus Nonstructural Protein NS5 Interacts with Mitochondrial Trifunctional Protein and Impairs Fatty Acid β-Oxidation

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Lipids are involved in various steps of viral infection, and viruses may alter lipid metabolism to facilitate efficient viral replication. To address whether long-chain fatty acid (LCFA) metabolism is affected by Japanese encephalitis virus (JEV) infection, the leading cause of viral encephalitis in Asia, we compared the oxygen consumption rate of mock- and JEV-infected cells cultured with or without LCFA. LCFA utilization was impaired in JEV-infected cells, and higher pro-inflammatory cytokine expression was induced when LCFA was the major energy source. JEV nonstructural protein 5 (NS5) interacted with mitochondrial trifunctional protein, an enzyme complex involved in LCFA β-oxidation, and the interaction impaired LCFA β-oxidation, enhanced cytokine production, and contributed to JEV pathogenesis. The M19 residue of NS5 is involved in its interaction with MTP and the recombinant JEV with NS5-M19A mutation was less able to block LCFA β-oxidation, induced lower levels of cytokine production and showed less neurovirulence and neuroinvasiveness than wild-type JEV. Thus, impaired LCFA β-oxidation and enhanced cytokine production induced by JEV NS5 may provide new insight into JEV virulence.

Vyšlo v časopise: Japanese Encephalitis Virus Nonstructural Protein NS5 Interacts with Mitochondrial Trifunctional Protein and Impairs Fatty Acid β-Oxidation. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004750
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004750

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