摘要Rabbit hemorrhagic disease virus(RHDV)is a member of the Caliciviridae family and cannot be propagated in vitro,which has impeded the progress of investigating its replication mechanism.Construction of an RHDV replicon system has recently provided a platform for exploring RHDV replication in host cells.Here,aided by this replicon system and using two-step affinity purification,we purified the RHDV replicase and identified its associated host factors.We identified rabbit nucleolin(NCL)as a physical link,which mediating the interaction between other RNA-dependent RNA polymerase(RdRp)-related host proteins and the viral replicase RdRp.We found that the overexpression or knockdown of NCL significantly increased or severely impaired RHDV repli-cation in RK-13 cells,respectively.NCL was identified to directly interact with RHDV RdRp,p16,and p23.Furthermore,NCL knockdown severely impaired the binding of RdRp to RdRp-related host factors.Collectively,these results indicate that the host protein NCL is essential for RHDV replication and acts as a physical link be-tween viral replicase and host proteins.