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.