THY1 inhibits the replication of ALV - J by diverting chNHE1 for proteasomal degradation

Avian leukosis virus subgroup J (ALV-J) induces myelocytoma and immunosuppression in infected chickens, thereby severely affecting the global poultry industry. Viruses generally utilize the host cellular machinery for their own replication. However, the interaction relationships between ALV-J and host proteins remain poorly understood. Thymocyte differentiation antigen 1 (THY1), a glycoprotein on the cell surface, plays a vital role in chicken memory. In this study, we investigated the tissue and cell distribution of THY1 in ALV-J-negative and ALV-J-positive chickens as well as in DF-1 cells, and explored the mechanism by which THY1 regulates ALV-J replication. We observed that the mRNA level of THY1 was the highest in the brain of ALV-J-negative chickens and in the lung tissue of ALV-J-positive chickens, respectively. Additionally, ALV-J infection of DF-1 cells had no impact on the distribution of THY1 in the cell membrane and cytoplasm. Moreover, the study revealed that THY1 suppresses ALV-J replication mainly by diverting its receptor, Na⁺/H⁺ exchanger type 1 (chNHE1), through interacting with chNHE1 and targeting it for proteasome-mediated degradation. This study is the first to report that a host protein inhibits ALV-J replication by influencing its receptor protein. This study provides valuable insights into the molecular mechanisms underlying ALV-J replication.