Key result
Enteroviral protease 2A plays a key role in viral replication and pathogenesis, including coxsackievirus-induced cardiomyopathy via dystrophin cleavage, by antagonizing innate immune responses.
Why the study?
The molecular mechanisms by which enteroviruses cause severe multiorgan complications such as myocarditis remain poorly understood, and studies of enteroviral protease 2Apro could reveal additional substrates associated with specific diseases.
Highlights the critical role of enteroviral protease 2A in viral pathogenesis and its specific implication in coxsackievirus-induced cardiomyopathy.
May implicate 2Apro/3Cpro inhibition in enteroviral myocarditis; leaves open targeted trials before practice change.
Enteroviruses (EV) are human pathogens commonly observed in children aged 0–5 years and adults. EV infections usually cause the common cold and hand-foot-and-mouth disease; however, more severe infections can result in multiorgan complications, such as polio, aseptic meningitis, and myocarditis. The molecular mechanisms by which enteroviruses cause these diseases are still poorly understood, but accumulating evidence points to two enterovirus proteases, 2Apro and 3Cpro, as the key players in pathogenesis. The protease 2Apro performs post-translational proteolytic processing of viral polyproteins and cleaves several host factors to evade antiviral immune responses and promote viral replication. It was also discovered that coxsackievirus-induced cardiomyopathy was caused by 2Apro-mediated cleavage of dystrophin in cardiomyocytes, indicating that cellular protein proteolysis may play a key role in enterovirus-associated diseases. Therefore, studies of 2Apro could reveal additional substrates that may be associated with specific diseases. Here, we discuss the genetic and structural properties of 2Apro and review how the protease antagonizes innate immune responses to promote viral replication, as well as novel substrates and mechanisms for 2Apro. We also summarize the current approaches for identifying the substrates of 2Apro to discover novel mechanisms relating to certain diseases.
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Liu et al. (2023) conducted a review in Enterovirus infections. Enteroviral protease 2A (2Apro) was evaluated. Enteroviral protease 2A plays a key role in viral replication and pathogenesis, including coxsackievirus-induced cardiomyopathy via dystrophin cleavage, by antagonizing innate immune responses.
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