GH inhibits ALV-J replication and restricts cell cycle by activating PI3K/Akt signaling pathway

Growth hormone (GH) plays a crucial role in growth, sexual maturity, and immunity in chickens. Avian leukosis virus subgroup J (ALV-J) is an exogenous tumorigenic retrovirus that primarily induces immunosuppression, growth retardation, decreased egg production, tumors formation, and even death in chickens. Previous studies have suggested that GH is involved in the regulation of innate immunity and inflammation. However, the specific role of GH in response to ALV-J remains unclear. In this study, we observed a significant upregulation of GH protein expression in the plasma of ALV infected chickens, and a marked increase in GH mRNA in ALV-J infected cells. We found that lower gp85 expression correlated with higher GH expression in immune tissues, suggesting that GH may inhibit gp85 expression. Additionally, GH overexpression enhanced the expression of interferons (IFN-α, IFN-β), interferon-stimulating genes (Mx1, ASCL1, CH25H), and pro-inflammatory factors (Mx1, ASCL1, CH25H) in DF-1 cells infected with ALV-J. GH also affected the cell cycle by regulating the expression of cell proliferation-related genes (p21, PCNA, Cyclin B2, Cyclin D1, Cyclin D2) and cell apoptosis-related genes (p53, Fas, Cyct, Caspase-1, Caspase-3, Caspase-8). More importantly, we found that GH restricted cell proliferation and apoptosis, and inhibited the replication of ALV-J by activating the PI3K/Akt signaling pathway in DF-1 cells. In conclusion, these results indicate GH plays a role in the antiviral response against the replication of ALV-J, providing evidence of an interaction between GH and the innate immunity in chickens.