Tetraspanin CD81 serves as a functional entry factor for porcine circovirus type 2 infection

作者：Junshuo Li, Lin Lv, Yanni Gao, Yangyang Sun, Juan Bai, Xianwei Wang, Haifen Sun, Ping Jiang · 发表于：Journal of Virology · 年份：2024 · DOI：10.1128/jvi.01408-24 · 被引用次数：4 · 研究领域：Animal Virus Infections Studies、Virus-based gene therapy research、RNA Interference and Gene Delivery

Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated disease, clinically resulting in immunosuppression and co-infections with other pathogens in infected pigs. The mechanism of PCV2 infection remains unclear. In this study, we firstly found that the tetraspanin CD81 in PK-15 cells interacts with PCV2 Cap protein by using virus overlay protein-binding assay combined with mass spectrometry. Knockdown of the CD81 significantly reduces the levels of the viral Cap mRNA and protein, and viral internalization in PK-15 cells. The critical interaction regions locate in the large extracellular loop (LEL) domain of CD81 and the CD loop region (82-91aa) of the Cap protein, and a polyclonal antibody against the CD81 LEL domain significantly inhibits PCV2 infection. The transmembrane proteoglycan Syndecan-1 interacts with both CD81 and PCV2 Cap, and co-operates with CD81 to promote PCV2 infection in PK-15 cells. Furthermore, CD81 facilitates RhoA activation and enhances the viral internalization and replication in PK-15 cells. It was concluded that the tetraspanin CD81 is a key host factor for PCV2 invasion into PK-15 cells, thus providing new insights into PCV2 life cycle and identifying a potential target for antiviral drug development.IMPORTANCEPorcine circovirus type 2 (PCV2), a significant economic pathogen in the swine industry, presents persistent challenges in its prevention and treatment. Despite extensive research, the mechanism of PCV...