title: Free fatty acids or high-concentration glucose enhances hepatitis A virus replication in association with a reduction in glucose-regulated protein 78 expression.
abstract: Although the interaction between host and hepatitis A virus (HAV) factors could lead to severe hepatitis A, the exact mechanism of acute liver failure caused by HAV infection is not yet fully understood. The effects of metabolic diseases such as dyslipidemia or diabetes mellitus on HAV replication are still unknown. Here, we examined the effects of free fatty acids or high-concentration glucose on HAV replication and the effects on mitogen-activated protein kinase signaling pathway-related genes in human hepatocytes. We discovered a novel effect of free fatty acids or high-concentration glucose on HAV replication in association with a reduction in the expression of glucose-regulated protein 78 (GRP78). We also observed that thapsigargin induced GRP78 expression and inhibited HAV replication. These findings may provide a new interpretation of the relationship between metabolic diseases and severity of hepatitis A and suggest a new understanding of the mechanism of severe HAV infection.
authors.affiliation: Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Nan
authors.initials: N
authors.lastname: Nwe Win
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. Electronic address: kandat-cib@umin.ac.jp.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan; Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamoto
authors.affiliation: Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
authors.affiliation: Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shirasawa
mesh_terms: D045744:Cell Line, Tumor; D015536:Down-Regulation; D000091342:Endoplasmic Reticulum Chaperone BiP; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006506:Hepatitis A / Q000150:complications / Q000821:virology*; D030041:Hepatitis A virus / Q000187:drug effects* / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008659:Metabolic Diseases / Q000150:complications; D019284:Thapsigargin / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D005230:Fatty Acids, Nonesterified; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D019284:Thapsigargin; D005947:Glucose
keywords: Acute liver failure; Free fatty acids; GRP78; Glucose; HAV