title: Human VAP-C negatively regulates hepatitis C virus propagation.
abstract: Human vesicle-associated membrane protein-associated protein (VAP) subtype A (VAP-A) and subtype B (VAP-B) are involved in the regulation of membrane trafficking, lipid transport and metabolism, and the unfolded protein response. VAP-A and VAP-B consist of the major sperm protein (MSP) domain, the coiled-coil motif, and the C-terminal transmembrane anchor and form homo- and heterodimers through the transmembrane domain. VAP-A and VAP-B interact with NS5B and NS5A of hepatitis C virus (HCV) through the MSP domain and the coiled-coil motif, respectively, and participate in the replication of HCV. VAP-C is a splicing variant of VAP-B consisting of the N-terminal half of the MSP domain of VAP-B followed by the subtype-specific frameshift sequences, and its biological function has not been well characterized. In this study, we have examined the biological functions of VAP-C in the propagation of HCV. VAP-C interacted with NS5B but not with VAP-A, VAP-B, or NS5A in immunoprecipitation analyses, and the expression of VAP-C inhibited the interaction of NS5B with VAP-A or VAP-B. Overexpression of VAP-C impaired the RNA replication of the HCV replicon and the propagation of the HCV JFH1 strain, whereas overexpression of VAP-A and VAP-B enhanced the replication. Furthermore, the expression of VAP-C was observed in various tissues, whereas it was barely detected in the liver. These results suggest that VAP-C acts as a negative regulator of HCV propagation and that the expression of VAP-C may participate in the determination of tissue tropism of HCV propagation.
authors.affiliation: Department of Molecular Virology, Research Institute for Microbial Diseases, Osaka University, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kukihara
authors.forename: Kohji
authors.initials: K
authors.lastname: Moriishi
authors.forename: Shuhei
authors.initials: S
authors.lastname: Taguwa
authors.forename: Hideki
authors.initials: H
authors.lastname: Tani
authors.forename: Takayuki
authors.initials: T
authors.lastname: Abe
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Mori
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takasuke
authors.initials: T
authors.lastname: Fukuhara
authors.forename: Akinobu
authors.initials: A
authors.lastname: Taketomi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Matsuura
mesh_terms: D002460:Cell Line; D015536:Down-Regulation; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000821:virology*; D006801:Humans; D011485:Protein Binding; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication; D012324:RNA-Dependent RNA Polymerase
chemical_list: D033921:Vesicular Transport Proteins; D017361:Viral Nonstructural Proteins; C114051:VAPA protein, human; C496748:VAPB protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase