Zika Virus Impairs Host NLRP3-mediated Inflammasome Activation in an NS3-dependent Manner

Immune Network
Eunji GimJe-Wook Yu

Abstract

Zika virus (ZIKV) is a mosquito-borne flavivirus associated with severe neurological disorders including Guillain-Barré syndrome and microcephaly. The host innate immune responses against ZIKV infection are essential for protection; however, ZIKV has evolved strategies to evade and antagonize antiviral responses via its nonstructural (NS) proteins. Here, we demonstrated that ZIKV infection unexpectedly inhibits NLRP3-dependent inflammasome activation in bone marrow-derived macrophages and mixed glial cells from mouse brain. ZIKV infection led to increased transcript levels of proinflammatory cytokines such as IL-1β and IL-6 via activating NF-κB signaling. However, ZIKV infection failed to trigger the secretion of active caspase-1 and IL-1β from macrophages and glial cells even in the presence of LPS priming or ATP costimulation. Intriguingly, ZIKV infection significantly attenuated NLRP3-dependent, but not absent in melanoma 2-dependent caspase-1 activation and IL-1β secretion from both cells. ZIKV infection further blocked apoptosis-associated speck-like protein containing a caspase recruitment domain oligomerization in LPS/ATP-stimulated macrophages. Interestingly, expression of ZIKV NS3 protein reduced NLRP3-mediated caspase...Continue Reading

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Citations

Feb 29, 2020·Pathogens·Aarón Oyarzún-ArrauRicardo Soto-Rifo

Related Concepts

Adenosine Triphosphate
Caspase
Flavivirus
Guillain-Barre Syndrome
Interleukin-1 beta
Interleukin-6
Lipopolysaccharides
Macrophage
Melanoma
Microcephaly

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