| Title | Roles of human apolipoprotein E in the infectivity and replication of hepatitis C virus genotype 2a |
|---|---|
| Author | Bo-Kyoung Jung1, Hye-Ran Kim1, Gyu-Nam Park1, Guangxiang Luo2,3, and Kyung-Soo Chang1* |
| Address | 1Department of Clinical Laboratory Science, Catholic University of Pusan, Busan 46252, Republic of Korea, 2Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky, USA , 3Department of Microbiology, Peking University College of Basic Medical Sciences, Beijing, P. R. China |
| Bibliography | Journal of Microbiology, 54(6),451-458, 2016, |
| DOI | 10.1007/s12275-016-6099-3 |
| Key Words | hepatitis C Virus (HCV), apolipoprotein E, small interfering RNA (siRNA), replication, genotypes |
| 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. |