title: Fatty acid biosynthesis is involved in the production of hepatitis B virus particles.
abstract: Hepatitis B virus (HBV) proliferates in hepatocytes after infection, but the host factors that contribute to the HBV lifecycle are poorly understood at the molecular level. We investigated whether fatty acid biosynthesis (FABS), which was recently reported to contribute to the genomic replication of hepatitis C virus, plays a role in HBV proliferation. We examined the effects of inhibitors of the enzymes in the FABS pathway on the HBV lifecycle by using recombinant HBV-producing cultured cells and found that the extracellular HBV DNA level, reflecting HBV particle production, was decreased by treatment with inhibitors suppressed the synthesis of long-chain saturated fatty acids with little cytotoxicity. The reduced HBV DNA level was reversed when palmitic acid, which is the product of fatty acid synthase (FAS) during FABS, was used simultaneously with the inhibitor. We also observed that the amount of intracellular HBV DNA in the cells was increased by FAS inhibitor treatment, suggesting that FABS is associated with HBV particle production but not its genome replication. This suggests that FABS might be a potent target for anti-HBV drug with a mode of action different from current HBV therapy.
authors.affiliation: Laboratory of Human Tumor Viruses, Institute for Virus Research, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507, Japan; Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho, Sakyoku, Kyoto 606-8501, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Okamura
authors.affiliation: Takeda Pharmaceutical Company Limited, Pharmaceutical Research Division, 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa 251-8555, Japan. Electronic address: yasunori.nio@takeda.com.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Nio
authors.affiliation: Laboratory of Human Tumor Viruses, Institute for Virus Research, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507, Japan; Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho, Sakyoku, Kyoto 606-8501, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Akahori
authors.affiliation: Laboratory of Human Tumor Viruses, Institute for Virus Research, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507, Japan.
authors.forename: Sulyi
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Department of Applied Biological Science, Tokyo University of Sciences, Noda 278-8510, Japan; CREST, Japan Science and Technology Agency (JST), Saitama 332-0012, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Watashi
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.affiliation: Laboratory of Human Tumor Viruses, Institute for Virus Research, Kyoto University, 53 Kawaharacho, Shogoin, Sakyoku, Kyoto 606-8507, Japan; Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho, Sakyoku, Kyoto 606-8501, Japan. Electronic address: mhijikat@virus.kyoto-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hijikata
mesh_terms: D004261:DNA Replication; D004279:DNA, Viral / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism*; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000378:metabolism* / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000821:virology*; D014771:Virion / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D005227:Fatty Acids
keywords: Fatty acid biosynthesis; Hepatitis B virus; Viral particle production