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Published on: June 28, 2018
Necrotizing myositis causes restrictive hypoventilation in a mouse model for human enterovirus 71 infection
Background:
Enterovirus 71 (EV71) infections are associated with a high prevalence of hand, foot and mouth disease (HFMD) in children and occasionally cause lethal complications. Most infections are self-limiting. However, resulting complications, including aseptic meningitis, encephalitis, poliomyelitis-like acute flaccid paralysis, and neurological pulmonary edema or hemorrhage, are responsible for the lethal symptoms of EV71 infection, the pathogenesis of which remain to be clarified.
Results:
In the present study, 2-week-old Institute of Cancer Research (ICR) mice were infected with a mouse-adapted EV71 strain. These infected mice demonstrated progressive paralysis and died within 12 days post infection (d.p.i.). EV71, which mainly replicates in skeletal muscle tissues, caused severe necrotizing myositis. Lesions in the central nervous system (CNS) and other tissues were not observed.
Conclusions:
Necrotizing myositis of respiratory-related muscles caused severe restrictive hypoventilation and subsequent hypoxia, which could explain the fatality of EV71-infected mice. This finding suggests that, in addition to CNS injury, necrotic myositis may also be responsible for the paralysis and death observed in EV71-infected mice.
Insights
Enterovirus 71 (EV71) causes hand, foot, and mouth disease. EV71 infection in mice led to muscle inflammation and respiratory failure, explaining paralysis and death, not just central nervous system damage.
Area of Science:
- Virology
- Pathogenesis
- Neurology
Background:
- Enterovirus 71 (EV71) is a significant cause of hand, foot, and mouth disease (HFMD) in children.
- EV71 infections can lead to severe, sometimes fatal, neurological complications.
- The exact mechanisms behind EV71's lethal effects remain unclear.
Purpose of the Study:
- To investigate the pathogenesis of Enterovirus 71 (EV71) infection in a mouse model.
- To determine the primary sites of EV71 replication and the resulting pathological changes.
- To elucidate the causes of mortality in EV71-infected mice.
Main Methods:
- Infection of 2-week-old Institute of Cancer Research (ICR) mice with a mouse-adapted EV71 strain.
- Observation of clinical signs, including paralysis and survival rates.
- Histopathological examination of tissues to identify viral replication and lesions, focusing on the central nervous system (CNS) and skeletal muscles.
Main Results:
- Infected mice exhibited progressive paralysis and mortality within 12 days post-infection.
- EV71 predominantly replicated in skeletal muscle tissues, causing severe necrotizing myositis.
- No significant lesions were observed in the central nervous system (CNS) or other organs.
Conclusions:
- Necrotizing myositis, particularly in respiratory muscles, led to severe hypoventilation and hypoxia, explaining the fatalities.
- The findings suggest that severe myositis, in addition to potential CNS injury, plays a critical role in the paralysis and death associated with EV71 infection.
- This highlights myositis as a key factor in EV71 pathogenesis and mortality.
