Zhaoyang Jing,Ling Wu,Yudi Pan,Liaoyuan Zhang,Xin Zhang,Da Shi,Hongyan Shi,Jianfei Chen,Zhaoyang Ji,Jiyu Zhang,Tingshuai Feng,Jin Tian,Li Feng

Vet Microbiol.2024 Mar 2:292:110036.doi: 10.1016/j.vetmic.2024.110036. Online ahead of print.

Abstract

Group A Rotavirus (RVA) is a major cause of diarrhea in infants and piglets. β2-microglobulin (β2 M), encoded by the B2M gene, serves as a crucial subunit of the major histocompatibility complex class I (MHC-I) molecules. β2 M is indispensable for the transport of MHC-I to the cell membrane. MHC-I, also known as swine leukocyte antigen class I (SLA-I) in pigs, presents viral antigens to the cell surface. In this study, RVA infection down-regulated β2 M expression in both porcine intestinal epithelial cells-J2 (IPEC-J2) and MA-104 cells. RVA infection did not down-regulate the mRNA level of the B2M gene, indicating that the down-regulation of β2 M occurred on the protein level. Mechanismly, RVA infection triggered β2 M aggregation in the endoplasmic reticulum (ER) and enhanced the Lys48 (K48)-linked ubiquitination of β2 M, leading to the degradation of β2 M through ERAD-proteasome pathway. Furthermore, we found that RVA infection significantly impeded the level of SLA-I on the surface, and the overexpression of β2 M could recover its expression. In this study, our study demonstrated that RVA infection degrades β2 M via ERAD-proteasome pathway, consequently hampering SLA-I expression on the cell surface. This study would enhance the understanding of the mechanism of how RVA infection induces immune escape.

Keywords: ERAD-proteasome pathway; K48-linked ubiquitination; RVA; SLA-I; β 2M.