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  • Phosphorylation and degradation of αB-crystallin during enterovirus infection facilitates viral replication and induces viral pathogenesis.

Phosphorylation and degradation of αB-crystallin during enterovirus infection facilitates viral replication and induces viral pathogenesis.

Oncotarget (2017-11-02)
Gabriel Fung, Jerry Wong, Feaven Berhe, Yasir Mohamud, Yuan Chao Xue, Honglin Luo
RESUMEN

Protein quality control (PQC) plays a key role in maintaining cardiomyocyte function and homeostasis, and malfunction in PQC is implicated in various forms of heart diseases. Molecular chaperones serve as the primary checkpoint for PQC; however, their roles in the pathogenesis of viral myocarditis, an inflammation of the myocardium caused by viral infection, are largely unknown. AlphaB-crystallin (CryAB) is the most abundant chaperone protein in the heart. It interacts with desmin and cytoplasmic actin to prevent protein misfolding and aggregation and to help maintain cytoskeletal integrity and cardiac function. Here we showed that coxsackievirus infection induced desminopathy-like phenotype of the myocardium, as characterized by the accumulation of protein aggregates and the disruption of desmin organization. We further demonstrated that CryAB was phosphorylated during early and downregulated at later stages of infection. Moreover, we showed that phosphorylated CryAB had a shorter half-life and was targeted to the ubiquitin-proteasome system for degradation. Lastly, we found that overexpression of CryAB significantly attenuated viral protein production and progeny release, indicating an anti-viral function for CryAB. Together, our results suggest a mechanism by which coxsackieviral infection induces CryAB degradation and loss-of-function, resulting in desmin aggregation, ultimately contributing to compromised cytoskeletal integrity and viral cardiomyopathy.

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Sigma-Aldrich
Z-Leu-Leu-Leu-al, ≥90% (HPLC)
Sigma-Aldrich
Anti-Amyloid Oligomer Antibody, αβ, oligomeric, serum, Chemicon®