Reticulon 3 interacts with NS4B of the hepatitis C virus and negatively regulates viral replication by disrupting NS4B self-interaction

摘要: Summary The non-structural protein 4B (NS4B) of the hepatitis C virus (HCV) is an endoplasmic reticulum (ER) membrane comprising two consecutive amphipathic α-helical domains (AH1 and AH2). Its self-oligomerization via AH2 domain required for formation membranous web that necessary viral replication. Previously, we reported host-encoded ER-associated reticulon 3 (RTN3) involved in replication-associated membranes (+)RNA enteroviruses during In this study, demonstrated second transmembrane region RTN3 competed for, bound to, NS4B, thus abolishing NS4B self-interaction leading to downregulation This interaction was mediated by crucial residues, lysine 52 tyrosine 63, AH2, regulated AH1 domain. The silencing Huh7 AVA5 cells harbouring HCV replicon enhanced replication HCV, which counteracted overexpression recombinant RTN3. synthesis RNA also increased siRNA-transfected human primary hepatocytes infected with derived from cell culture. Our results acted as a restriction factor limit HCV.