The selective autophagic degradation of avian metapneumovirus subgroup C M2-2 protein via SQSTM1 suppresses viral replication.

Avian metapneumovirus subgroup C (aMPV/C) is an emerging pathogen that causes acute respiratory infection in chickens and turkeys. Sequestosome 1 (SQSTM1), a selective autophagy receptor, regulates cellular activity or viral replication by recognizing ubiquitinated substrates. Here, we found that SQSTM1 expression inhibits aMPV/C replication through selective autophagy. In particular, SQSTM1 interacts with the aMPV/C M2-2 protein via its PB1 domain, and by recognizing a ubiquitinated lysine at position 67 of viral M2-2 protein. This recognition leads to the autophagic degradation of the aMPV/C M2-2 protein, suppressing viral replication.