The alternatively spliced porcine FcγRI regulated PRRSV-ADE infection and proinflammatory cytokine production

Receptors for the Fc region of IgG (Fc gamma Rs) play a key role in protecting the immune system and host from infection. In this study, we described the cloning, sequencing and characterization of porcine Fc gamma RI, and reported six different Fc gamma RI isoforms, four of which have never been reported before. Further analysis revealed that Fc gamma R isoforms are generated by alternative splicing mechanisms, including two membrane isoforms and four soluble isoforms. Importantly, we found Fc gamma RI splice variants differentially influence PRRSV antibody-dependent enhancement (ADE) effects. Membrane pCD64-T1 promotes endocytosis of the PRRSV-antibody complex to enhance PRRSV replication, and soluble pCD64-T3 has no ADE effect on PRRSV proliferation, but shows an inflammation enhancement effect. The differential expression of selective splicing in primary PAM cells and 3D4/21 cell lines are altered and regulated by PRRSV infection and inflammatory environment. Our results indicated that porcine Fc gamma RI plays dual regulatory roles in PRRSV multiplication and PRRSV inflammation process by the alternatively spliced mechanism, which will be a new target in PRRSV prevention and control.