DNMT3B inhibits PCV2 replication via targeting TMEM37 to regulate Ca^2 + influx in PK15 cells

Porcine circovirus type 2 (PCV2) is the main pathogen causing postweaning multisystemic wasting syndrome, which leads to enormous losses for porcine industry. However, the regulatory mechanism of PCV2 replication in host cells remains not been clarified. Here, pig DNMT3B was identified as be a host regulator associated with PCV2 infection via RNA-seq analysis. We demonstrated that upregulation of DNMT3B expression can effectively inhibit PCV2 replication in PK15 cells. Besides, TMEM37 acts as a key downstream target of DNMT3B in PCV2-infected PK15 cells. TMEM37 knockdown significantly slowed Ca²⁺ influx, and thus inhibited PCV2 replication. Taken together, DNMT3B is required for the PCV2-based infection regulation in host cells. Our findings indicated that DNMT3B inhibits PCV2 replication via targeting TMEM37 to regulate Ca²⁺ influx in PK15 cells, which offering a theoretical foundation for the use of this gene as a key biomarker for breeding strategies seeking to improve porcine disease resistance.