An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6, facilitate hepatitis C virus replication.
Hepatitis C virus (HCV) is a positive-sense single-stranded RNA virus. NS5b is an RNA-dependent RNA polymerase that polymerizes the newly synthesized RNA. HCV likely uses host proteins for its replication, similar to other RNA viruses. To identify the cellular factors involved in HCV replication, we searched for cellular proteins that interact with the NS5b protein. HnRNP A1 and septin 6 proteins were identified by coimmunoprecipitation and yeast two-hybrid screening, respectively. Interestingly, septin 6 protein also interacts with hnRNP A1. Moreover, hnRNP A1 interacts with the 5'-nontranslated region (5' NTR) and the 3' NTR of HCV RNA containing the cis-acting elements required for replication. Knockdown of hnRNP A1 and overexpression of C-terminally truncated hnRNP A1 reduced HCV replication. In addition, knockdown of septin 6 and overexpression of N-terminally truncated septin 6 inhibited HCV replication. These results indicate that the host proteins hnRNP A1 and septin 6 play important roles in the replication of HCV through RNA-protein and protein-protein interactions.
Kim
Chon Saeng
CS
PBC, Department of Life Science, Pohang University of Science and Technology, San 31, Hyoja-Dong, Pohang 790-784, Republic of Korea.
Seol
Su Kyoung
SK
Song
Ok-Kyu
OK
Park
Ji Hoon
JH
Jang
Sung Key
SK
D020413:3' Untranslated Regions / Q000378:metabolism; D020121:5' Untranslated Regions / Q000378:metabolism; D002460:Cell Line; D003598:Cytoskeletal Proteins; D019204:GTP-Binding Proteins / Q000502:physiology*; D020868:Gene Silencing; D016174:Hepacivirus / Q000502:physiology*; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D011485:Protein Binding; D012367:RNA, Viral / Q000378:metabolism; D058112:Septins; D020798:Two-Hybrid System Techniques; D014779:Virus Replication
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D003598:Cytoskeletal Proteins; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D012367:RNA, Viral; D019204:GTP-Binding Proteins; C436485:SEPTIN6 protein, human; D058112:Septins