title: Reactive oxygen species promote heat shock protein 90-mediated HBV capsid assembly.
abstract: Hepatitis B virus (HBV) infection induces reactive oxygen species (ROS) production and has been associated with the development of hepatocellular carcinoma (HCC). ROS are also an important factor in HCC because the accumulated ROS leads to abnormal cell proliferation and chromosome mutation. In oxidative stress, heat shock protein 90 (Hsp90) and glutathione (GSH) function as part of the defense mechanism. Hsp90 prevents cellular component from oxidative stress, and GSH acts as antioxidants scavenging ROS in the cell. However, it is not known whether molecules regulated by oxidative stress are involved in HBV capsid assembly. Based on the previous study that Hsp90 facilitates HBV capsid assembly, which is an important step for the packing of viral particles, here, we show that ROS enrich Hsp90-driven HBV capsid formation. In cell-free system, HBV capsid assembly was facilitated by ROS with Hsp90, whereas it was decreased without Hsp90. In addition, GSH inhibited the function of Hsp90 to decrease HBV capsid assembly. Consistent with the result of cell-free system, ROS and buthionine sulfoximine (BS), an inhibitor of GSH synthesis, increased HBV capsid formation in HepG2.2.15 cells. Thus, our study uncovers the interplay between ROS and Hsp90 during HBV capsid assembly.
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: yumshak@naver.com.
authors.forename: Yoon Sik
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: suruk@naver.com.
authors.forename: Hyun Wook
authors.initials: HW
authors.lastname: Seo
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: drjung@snu.ac.kr.
authors.forename: Guhung
authors.initials: G
authors.lastname: Jung
mesh_terms: D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002213:Capsid / Q000502:physiology; D002474:Cell-Free System; D004279:DNA, Viral / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000502:physiology*; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D018384:Oxidative Stress; D011487:Protein Conformation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019065:Virus Assembly / Q000187:drug effects / Q000502:physiology*
chemical_list: D004279:DNA, Viral; D018841:HSP90 Heat-Shock Proteins; D017382:Reactive Oxygen Species; D019328:Buthionine Sulfoximine; D005978:Glutathione
keywords: Capsid assembly; Core protein 149; Glutathione; Heat shock protein 90; Hepatitis B virus; Reactive oxygen species