Related Experiment Video
Updated: Jul 1, 2025
Assays for the Specific Growth Rate and Cell-binding Ability of Rotavirus
Published on: January 28, 2019
Rotavirus infection inhibits SLA-I expression on the cell surface by degrading β2 M via ERAD-proteasome pathway
Zhaoyang Jing1, Ling Wu1, Yudi Pan1
1State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Harbin, People's Republic of China.
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.
Insights
Group A Rotavirus (RVA) infection reduces beta2-microglobulin (β2M) protein levels by triggering its degradation through the ERAD-proteasome pathway. This leads to decreased swine leukocyte antigen class I (SLA-I) on cell surfaces, aiding viral immune escape.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Group A Rotavirus (RVA) is a significant cause of diarrhea in infants and piglets.
- Beta2-microglobulin (β2M) is essential for Major Histocompatibility Complex class I (MHC-I) surface expression, presenting viral antigens.
- MHC-I is known as swine leukocyte antigen class I (SLA-I) in pigs.
Purpose of the Study:
- To investigate the effect of RVA infection on β2M expression in porcine intestinal epithelial cells (IPEC-J2) and MA-104 cells.
- To elucidate the mechanism by which RVA influences β2M levels.
- To determine the impact of RVA-induced β2M down-regulation on SLA-I surface expression.
Main Methods:
- RVA infection of IPEC-J2 and MA-104 cell lines.
- Analysis of β2M mRNA and protein levels.
- Investigation of β2M aggregation and ubiquitination in the endoplasmic reticulum (ER).
- Assessment of ER-associated degradation (ERAD) and proteasome pathway involvement.
- Measurement of cell surface SLA-I expression.
Main Results:
- RVA infection significantly down-regulated β2M protein expression, but not B2M mRNA levels, in both cell types.
- RVA infection induced β2M aggregation in the ER and increased its K48-linked ubiquitination, targeting it for ERAD-proteasome degradation.
- RVA infection markedly reduced surface SLA-I levels.
- Overexpression of β2M restored SLA-I surface expression.
Conclusions:
- RVA infection degrades β2M via the ERAD-proteasome pathway.
- The reduction in β2M consequently impairs SLA-I surface expression.
- This mechanism contributes to RVA-induced immune escape by limiting viral antigen presentation.
More Related Videos
Related Concept Videos
02:28Leaky Scanning
02:15Experimental RNAi
02:30siRNA - Small Interfering RNAs
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...