biostudies-literatureUnknown27(3)Pang JDNational Natural Science Foundation of China<i>Trichinella spiralis</i> infection is associated with the formation of cysts within host skeletal muscle cells, thereby enabling immune evasion and subsequent growth and development; however, the pathogenic factors involved in this process and their mechanisms remain elusive. Here, we found that <i>Ts</i>-RNF secreted by <i>T. spiralis</i> is required for its growth and development in host cells. Further study revealed that <i>Ts</i>-RNF functions as an E3 ubiquitin ligase that targets the UBA domain of SQSTM1/p62 by forming K63-type ubiquitin chains. This modification interferes with autophagic flux, leading to impaired mitochondrial clearance and abnormal myotube differentiation and fusion. Our results established that <i>T. spiralis</i> increases its escape by interfering with host aiScience109102https://www.ebi.ac.uk/biostudies/studies/S-EPMC10877949biostudies-literature<i>Trichinella spiralis</i> inhibits myoblast differentiation by targeting SQSTM1/p62 with a secreted E3 ubiquitin ligase.PMC10877949Liu YLiu XLXu NDong ZJPang JDJin XMBoireau PLiu MYVallee IDing Jfalse<i>Trichinella spiralis</i> inhibits myoblast differentiation by targeting SQSTM1/p62 with a secreted E3 ubiquitin ligase.<i>Trichinella spiralis</i> infection is associated with the formation of cysts within host skeletal muscle cells, thereby enabling immune evasion and subsequent growth and development; however, the pathogenic factors involved in this process and their mechanisms remain elusive. Here, we found that <i>Ts</i>-RNF secreted by <i>T. spiralis</i> is required for its growth and development in host cells. Further study revealed that <i>Ts</i>-RNF functions as an E3 ubiquitin ligase that targets the UBA domain of SQSTM1/p62 by forming K63-type ubiquitin chains. This modification interferes with autophagic flux, leading to impaired mitochondrial clearance and abnormal myotube differentiation and fusion. Our results established that <i>T. spiralis</i> increases its escape by interfering with host a2024-01-01T00:00:00Z2024 Mar2026-06-18T06:53:26.904Z2025-04-19T07:35:51.077ZS-EPMC108779493838025310.1016/j.isci.2024.109102