Research Papers:

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

Gabriel Fung, Jerry Wong, Feaven Berhe, Yasir Mohamud, Yuan Chao Xue and Honglin Luo _

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Oncotarget. 2017; 8:74767-74780. https://doi.org/10.18632/oncotarget.20366

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Gabriel Fung1, Jerry Wong2, Feaven Berhe1, Yasir Mohamud1, Yuan Chao Xue1 and Honglin Luo1

1Centre for Heart Lung Innovation, St. Paul’s Hospital and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

2Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Pathology, School of Medicine, University of California San Diego, La Jolla, CA, USA

Correspondence to:

Honglin Luo, email: [email protected]

Keywords: alphaB-crystallin, viral myocarditis, dilated cardiomyopathy, coxsackievirus, desmin

Received: May 18, 2017     Accepted: July 25, 2017     Published: August 19, 2017


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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