Supplemental materials for "Duck circovirus regulates the expression of duck CLDN2 protein by activating the MAPK-ERK pathway to affect its adhesion and infection".docx

Although DuCV poses a widespread infection and a serious hazard to the duck industry, the molecular mechanisms underlying DuCV infection and transmission remain elusive. Here, we initiallydemonstrated vertical transmission of DuCV through female breeding ducks by simulating natural infection. Furthermore,a differentially expressed membrane protein CLDN2was identified on the DuCV-infected oviductof female ducks, and its extracellular loop structural domains EL1 and EL2 were identified as the interaction sites of DuCVCapproteins. Moreover, the binding of DuCV Cap to CLDN2 triggered the intracellular MAPK-ERK pathway and activated the downstream transcription factor SP5.Importantly, we demonstrated thatintracellularCap also interacts with SP5, leading to upregulation of CLDN2 transcription and facilitating enhanced adherence of DuCV to target tissue such as the oviduct, thereby promoting viral infection and transmission. Our study sheds light on the molecular mechanisms underlying vertical transmission of DuCV, highlighting CLDN2 as a promising and universally applicable target for drug development against DuCV infection.