title: Roles of human apolipoprotein E in the infectivity and replication of hepatitis C virus genotype 2a.
abstract: Hepatitis C virus (HCV) infection is associated with lipoproteins, and apolipoprotein E (apoE) plays an essential role in infectious HCV particles. Although the role of apoE in HCV infection is well known, its role in the replication of HCV remains unclear. The aims of this study were to determine the role of apoE in the RNA replication of major HCV genotypes 1b and 2a, and to determine whether this role is HCVgenotype-dependent using HCV genotype 1b replicon cells and HCV genotype 2a producing (HP) cells. HCV infection was blocked in Huh7.5 cells treated with low-density lipoproteins, very low-density lipoproteins, or apoE3. An apoE3-specific monoclonal antibody also efficiently neutralized HCV infectivity, and HCV infection was dramatically suppressed by the knockdown of apoE expression with an apoE-specific small interfering RNA, suggesting a requirement for apoE in infectious HCV particles. HCV RNA replication was not affected in HP cells treated with each apoE isoform or transfected with apoE-specific siRNAs. However, the knockdown of apoE expression suppressed RNA replication of HCV genotype 1b. The siRNA-mediated knockdown of apoE, apoA1, and apoB expression also suppressed the RNA replication of HCV genotype 1b, but not that of HCV genotype 2a. Taken together, these findings indicate that apoE plays an important role in HCV genotype 2a infection and in HCV genotype 1b RNA replication, but not in the replication of HCV genotype 2a. These results provide important information for the future development of HCV-genotypespecific anti-HCV agents.
authors.affiliation: Department of Clinical Laboratory Science, Catholic University of Pusan, Busan, 46252, Republic of Korea.
authors.forename: Bo-Kyoung
authors.initials: BK
authors.lastname: Jung
authors.affiliation: Department of Clinical Laboratory Science, Catholic University of Pusan, Busan, 46252, Republic of Korea.
authors.forename: Hye-Ran
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Clinical Laboratory Science, Catholic University of Pusan, Busan, 46252, Republic of Korea.
authors.forename: Gyu-Nam
authors.initials: GN
authors.lastname: Park
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky, USA.|Department of Biological Science, The Florida State University, Tallahassee, Florida, USA.|Department of Microbiology, Peking University College of Basic Medical Sciences, Beijing, P. R. China.
authors.forename: Guangxiang
authors.initials: G
authors.lastname: Luo
authors.affiliation: Department of Clinical Laboratory Science, Catholic University of Pusan, Busan, 46252, Republic of Korea. kschang@cup.ac.kr.
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Chang
mesh_terms: D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006526:Hepatitis C / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D013045:Species Specificity; D014779:Virus Replication
chemical_list: C000612345:ApoE protein, human; D001057:Apolipoproteins E; D004279:DNA, Viral
keywords: apolipoprotein E; genotypes; hepatitis C Virus (HCV); replication; small interfering RNA (siRNA)