National Natural Science Foundation of China (NSFC)
中国
引用
ジャーナル: iScience / 年: 2025 タイトル: Structural basis for DNA replication by the African swine fever virus polymerase. 著者: Ziwei Hu / Yongjie SunKang / Zhiheng Liu / Lihong Huang / Wenbao Qi / Renhong Yan / 要旨: African swine fever virus (ASFV) devastates swine herds and lacks widely available antivirals. We show that the ASFV DNA polymerase beta (Pol β; gene ) localizes to viral replication factories and ...African swine fever virus (ASFV) devastates swine herds and lacks widely available antivirals. We show that the ASFV DNA polymerase beta (Pol β; gene ) localizes to viral replication factories and is required for viral replication. Cryo-electron microscopy structures of Pol β in apo and double-stranded DNA (dsDNA)-bound states reveal pronounced conformational flexibility that enables transitions between functional states. Binding to dsDNA promotes higher-order oligomerization that is essential for catalytic activity, as demonstrated by structure-guided mutagenesis and biochemical assays. These findings define the structural basis of ASFV genome synthesis, highlight the functional significance of Pol β during viral replication, and provide a framework for polymerase-targeted antiviral discovery.