title: AAM-B Interacts with Nonstructural 4B and Regulates Hepatitis C Virus Propagation.
abstract: Hepatitis C virus (HCV) usurps host cellular lipid metabolism for production of infectious virus particles. Recently, we have screened a siRNA library targeting host factors that control lipid metabolism and lipid droplet (LD) formation in cell culture grown HCV (HCVcc)-infected cells. Of 10 final candidates, we selected the gene encoding AAM-B for further characterization. We showed that siRNA-mediated knockdown of AAM-B impaired HCV propagation in Jc1-infected cells. More precisely, knockdown of AAM-B abrogated production of infectious HCV particles in both Jc1 RNA electroporated cells and Jc1-infected cells. It is worth noting that knockdown of AAM-B exerted no effect on lipid droplet formation. Moreover, AAM-B interacted with nonstructural 4B (NS4B) through the C-terminal region of NS4B. Protein interplay between AAM-B and NS4B was verified in the context of HCV replication. Using either transient or stable expression of AAM-B, we verified that AAM-B colocalized with NS4B in the cytoplasm. Immunofluorescence data further showed that AAM-B might be involved in recruitment of NS4B to sites in close proximity to LDs to facilitate HCV propagation. Collectively, this study provides new insight into how HCV utilizes cellular AAM-B to facilitate viral propagation.
authors.affiliation: National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym University, Anyang, Korea.
authors.forename: Eun-Mee
authors.initials: EM
authors.lastname: Park
authors.affiliation: National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym University, Anyang, Korea.
authors.forename: Yun-Sook
authors.initials: YS
authors.lastname: Lim
authors.affiliation: School of Science and Biotechnology, Korea University, Seoul, Korea.
authors.forename: Byung-Yoon
authors.initials: BY
authors.lastname: Ahn
authors.affiliation: National Research Laboratory of Hepatitis C Virus and Ilsong Institute of Life Science, Hallym University, Anyang, Korea.
authors.forename: Soon B
authors.initials: SB
authors.lastname: Hwang
mesh_terms: D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology; D050356:Lipid Metabolism / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C080107:NS4B protein, flavivirus; D034741:RNA, Small Interfering; D017361:Viral Nonstructural Proteins; C000607000:AAM-B protein, human; D008780:Methyltransferases