Porcine FcγRIIb mediated PRRSV ADE infection through inhibiting IFN-β by cytoplasmic inhibitory signal transduction

Antibody-dependent enhancement (ADE) in porcine reproductive and respiratory syndrome virus (PRRSV) infection is a significant obstacle to the development of effective vaccines for controlling PRRS. Our previous results have demonstrated that porcine Fc gamma RIIb (poFc gamma RIIb) play an important role in mediating ADE of PRRSV infection in vitro. However, the underlying mechanisms involved in poFc gamma RIIb mediated-ADE are still not clear. In this study, MARC-145 cel1 lines stably expressing mutated poFc gamma RIIb (MARC-poFc gamma RIIb-T and MARC-poFc gamma RIIb-CT) in cytoplasm were established and the capacity of poFc RIIb mutants in mediating ADE of PRRSV was investigated. Our results showed that removal of cytoplasmic domain or disruption the tyrosine residue within ITIM (immunoreceptor tyrosine-based inhibition motif) of the poFc gamma RIIb abolished the ability of poFc gamma RIIb to mediate ADE of PRRSV. Furthermore, we found that SHIP1 and TBK1 were involved in poFc RIIb-mediated ADE of PRRSV infection. Taken together, our findings indicated that poFc RIIb mediated the ADE pathway of PRRSV infection through recruiting SHIP-1, which further inhibited of TBK-1-IRF3-IFN-beta signaling pathway to enhance PRRSV infection. These findings will contribute to the molecular mechanism of ADE infection and provide some implications for vaccine development. (C) 2019 Elsevier B.V. All rights reserved.