Pyroptosis induced by enterovirus 71 and coxsackievirus B3 infection affects viral replication and host response

Area of Science:

• Virology
• Immunology
• Cellular Biology

Background:

• Enterovirus 71 (EV71) causes severe neurological complications in hand, foot, and mouth disease (HFMD).
• Pyroptosis, a programmed inflammatory cell death, is implicated in viral pathogenesis but its role in EV71 infection is unclear.
• Enteroviruses are a significant public health concern, necessitating research into their mechanisms of disease.

Purpose of the Study:

• To investigate the role of pyroptosis in the pathogenesis of Enterovirus 71 (EV71) and coxsackievirus B3 (CVB3) infections.
• To evaluate the therapeutic potential of caspase-1 inhibitors against EV71 and CVB3 infections.

Main Methods:

• EV71 and CVB3 infection of cell cultures and mouse models.
• Measurement of caspase-1 activation, IL-1β, IL-18, and NLRP3 expression.
• Assessment of viral replication and disease severity in the presence and absence of caspase-1 inhibitors.

Main Results:

• EV71 infection induced caspase-1 activation, leading to increased IL-1β and IL-18 secretion.
• Caspase-1 inhibition significantly improved systemic responses and suppressed EV71 replication in mouse brains.
• CVB3 infection also activated pyroptosis, with caspase-1 inhibition reducing viral replication and improving overall conditions in infected mice.

Conclusions:

• Pyroptosis is a key mechanism in the pathogenesis of both EV71 and CVB3 infections.
• Caspase-1 inhibitors demonstrate therapeutic benefits by reducing viral replication and mitigating disease severity.
• Targeting pyroptosis via caspase-1 inhibition presents a promising strategy for treating enterovirus infections.