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Published on: March 2, 2014
MDA5 attenuate autophagy in chicken embryo fibroblasts infected with IBDV
1College of Veterinary Medicine, Northeast Agricultural University, Harbin, People's Republic of China.
Abstract:
1. The role of melanoma differentiation-associated protein 5 (MDA5) in infectious bursal disease virus (IBDV)-induced autophagy was studied in chicken embryos.2. Chicken embryo fibroblasts (CEF) were used as the research model and small interfering RNA (siRNA), western blot, indirect enzyme-linked immunosorbent assay (ELISA), real-time fluorescence quantitative polymerase chain reaction (PCR) and transmission electron microscopy were used to detect autophagy, IBDV replication, CEF damage, and activation of both MDA5 and its signalling pathway.3. The results showed that CEF infected with IBDV activated the intracellular MDA5 signalling pathway and caused autophagy via inactivation of the AKT/mTOR pathway. While autophagy promotes IBDV proliferation, MDA5 weakens IBDV-induced CEF autophagy thus inhibiting IBDV replication and protecting CEF cells.4. The results indicated that chMDA5 can be activated by IBDV and attenuate CEF autophagy caused by IBDV infection, thereby inhibiting IBDV replication. This study provided a foundation for further exploring the relationship between viruses, autophagy and the pathogenic mechanism of the MDA5 pathway involved in IBDV.
Insights
Melanoma differentiation-associated protein 5 (MDA5) activation inhibits infectious bursal disease virus (IBDV) replication by weakening IBDV-induced autophagy in chicken cells. This finding clarifies MDA5
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Autophagy plays a complex role in viral infections, potentially promoting or inhibiting viral replication.
- Melanoma differentiation-associated protein 5 (MDA5) is an innate immune sensor involved in detecting viral RNA.
Purpose of the Study:
- To investigate the role of chicken MDA5 (chMDA5) in autophagy induced by infectious bursal disease virus (IBDV).
- To elucidate the mechanism by which chMDA5 influences IBDV replication and chicken embryo fibroblast (CEF) survival.
Main Methods:
- Chicken embryo fibroblasts (CEF) were infected with IBDV.
- Techniques included small interfering RNA (siRNA) for gene silencing, western blot, ELISA, real-time PCR, and transmission electron microscopy.
- Autophagy, viral replication, cell damage, and MDA5 pathway activation were assessed.
Main Results:
- IBDV infection activated the intracellular MDA5 signalling pathway and induced autophagy via AKT/mTOR inactivation.
- While autophagy promoted IBDV proliferation, chMDA5 attenuated IBDV-induced autophagy, thereby inhibiting viral replication.
- chMDA5 activation by IBDV protected CEF cells from damage.
Conclusions:
- chMDA5 activation by IBDV inhibits viral replication by attenuating IBDV-induced autophagy.
- This study deepens the understanding of the interplay between viruses, autophagy, and the MDA5 pathway in viral pathogenesis.
