Encephalomyelitis is a well-known complication of
hand, foot, and mouth disease (HFMD) due to Enterovirus 71 (EV71)
infection.
Viral RNA/
antigens could be detected in the central nervous system (CNS) neurons in fatal
encephalomyelitis but the mechanisms of neuronal cell death is not clearly understood. We investigated the role of absent in
melanoma 2 (AIM2)
inflammasome in neuronal cell death, and its relationship to viral replication. Our transcriptomic analysis, RT-qPCR, Western blot, immunofluorescence and flow cytometry studies consistently showed AIM2 gene up-regulation and
protein expression in EV-A71-infected SK-N-SH cells. Downstream AIM2-induced genes, CARD16, caspase-1 and IL-1β were also up-regulated and caspase-1 was activated to form cleaved caspase-1 p20 subunits. As evidenced by
7-AAD positivity, pyroptosis was confirmed in infected cells. Overall, these findings have a strong correlation with decreases in viral titers, copy numbers and
proteins, and reduced proportions of infected cells. AIM2 and
viral antigens were detected by immunohistochemistry in infected neurons in inflamed areas of the CNS in EV-A71
encephalomyelitis. In infected AIM2-knockdown cells, AIM2 and related downstream gene expressions, and pyroptosis were suppressed, resulting in significantly increased
virus infection. These results support the notion that AIM2
inflammasome-mediated pyroptosis is an important mechanism of neuronal cell death and it could play an important role in limiting EV-A71 replication.