Autophagy-mediated TET2 degradation by ALV-J Env protein suppresses innate immune activation to promote viral replication.

ABSTRACT: Avian leukosis virus subgroup J (ALV-J) poses a significant threat to the poultry industry; yet, our understanding of its replication and pathogenic mechanisms is limited. The Ten-Eleven Translocation 2 (TET2) is an indispensable regulatory factor in active DNA demethylation and immune response regulation. This study reports a significant and time-dependent decrease in TET2 levels following ALV-J infection and shows that the reduction of TET2 protein is mediated by the autophagy pathway. Mechanistically, we found that the accumulation of the Env protein at the late stages of ALV-J infection triggers autophagy, which, in turn, causes the TET2 protein to be exported from the nucleus and subsequently degraded in the cytoplasm. Using CRISPR-Cas9 technology, we generated TET2-deficient chicken

SUBMITTER: Chen S 

PROVIDER: S-EPMC11852998 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature