Trichinella spiralis inhibits myoblast differentiation by targeting SQSTM1/p62 with a secreted E3 ubiquitin ligase
Jian da Pang,
Xue min Jin,
Yi Liu,
Zi jian Dong,
Jing Ding,
Pascal Boireau,
Isabelle Vallée,
Ming yuan Liu,
Ning Xu,
Xiao lei Liu
Affiliations
Jian da Pang
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin 130062, China
Xue min Jin
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin 130062, China
Yi Liu
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin 130062, China
Zi jian Dong
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin 130062, China
Jing Ding
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin 130062, China
Pascal Boireau
Ecole Nationale Vétérinaire d’Alfort, Laboratoire de Santé Animale, BIPAR, 94700 Maisons-Alfort, France
Isabelle Vallée
Ecole Nationale Vétérinaire d’Alfort, Laboratoire de Santé Animale, BIPAR, 94700 Maisons-Alfort, France
Ming yuan Liu
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin 130062, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225000, China
Ning Xu
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin 130062, China; Corresponding author
Xiao lei Liu
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin 130062, China; Corresponding author
Summary: Trichinella spiralis 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 Ts-RNF secreted by T. spiralis is required for its growth and development in host cells. Further study revealed that Ts-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 T. spiralis increases its escape by interfering with host autophagy via the secretion of an E3 ubiquitin ligase.
