Growth Arrest and DNA Damage Protein 45A Promotes PPRV Replication via the Downregulation of TBK1 Expression to...

Peste des petits ruminants virus (PPRV) is a highly contagious pathogen that severely impacts goats and sheep due to its high contagiousness and pathogenicity. Viruses rely on host proteins for their pathogenicity and replication, but the specific mechanisms facilitating PPRV replication by host proteins remain poorly understood. In this study, we identified goat growth arrest and DNA damage protein 45A (GADD45A) as a positive regulator of PPRV replication. Overexpression of GADD45A enhances PPRV replication, while its knockdown significantly inhibits PPRV replication. Furthermore, GADD45A suppresses SeV- or Poly(I:C)-induced IFN-β promoter and ISRE activation in a dose-dependent manner, as well as the transcription of interferon-stimulated genes (ISGs). We also demonstrate that goat GADD45A interacts with TANK-binding kinase 1 (TBK1), leading to the downregulation of TBK1 expression. Co-immunoprecipitation and confocal microscopy confirmed that GADD45A interacts with the PPRV V protein. Both GADD45A and V synergistically inhibit IFN-β promoter activation and TBK1 expression, thereby promoting PPRV replication. Our findings suggest that GADD45A promotes PPRV replication by downregulating TBK1, offering new insights into host proteins that counteract innate immune responses during PPRV infection. These findings offer valuable insights into the role of host proteins in viral replication and immune evasion, shedding new light on how PPRV antagonizes innate immunity.