Inhibition of Abl or Src tyrosine kinase decreased porcine circovirus type 2 production in PK15 cells.

Porcine circovirus type 2 (PCV2) causes huge economic losses in the global swine industry and has a complex and poorly understood virus-host interaction mechanism. We reported that the C-terminal of the capsid protein of all PCV2 isolates shared a strictly conserved PXXP motif that may interact with SH3 domain-containing tyrosine kinases; however, its roles in PCV2 cell entry and replication remain unknown. In this study, we determined that mRNA levels of two SH3 domain-containing tyrosine kinases family (Abl and Src) had distinct profiles (wild-type and PXXP-mutated) during PCV2 infections of PK15 cells. Therefore, we hypothesized that activities of tyrosine kinases (Abl and Fyn) in PK15 cells may be hijacked by PCV2 via its PXXP motif of the Cap, to favor virus replication. Specific inhibitors PP2 of Lck/Fyn and STI-571 of Abl family kinases decreased viral production through suppression of DNA and Cap synthesis at the replication stage. However, based on indirect immunofluorescence assay (IFA), entry of PCV2 virus-like particles (VLPs) into PK15 cells was not altered. Elucidating mechanisms of PCV2-host interactions should provide new insights for development of new compounds to prevent or reduce PCV2 infections.