PMID:23302887

Citation	Kumar, M, Roe, K, Orillo, B, Muruve, DA, Nerurkar, VR, Gale, M Jr and Verma, S' (2013) Inflammasome adaptor protein apoptosis-associated speck-like protein containing CARD (ASC) is critical for the immune response and survival in West Nile virus encephalitis. J. Virol. '
Abstract	West Nile virus (WNV) is a neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis in humans. WNV-induced innate immune response including production of antiviral cytokines is critical for controlling virus infection. The adaptor protein ASC mediates a critical step in innate immune signaling by bridging the interaction between the pathogen recognition receptors and caspase-1 in inflammasome complexes but its role in WNV immunopathogenesis is not defined. Herein, we demonstrate that ASC is essential for IL-1β production and development of effective host immunity against WNV. ASC-deficient mice exhibited increased susceptibility to WNV infection and reduced survival was associated with enhanced virus replication in the peripheral tissues and CNS. Infection of cultured bone marrow derived dendritic cells showed that ASC was essential for the activation of caspase-1, a key component of inflammasome assembly. ASC(-/-) mice exhibited attenuated levels of pro-inflammatory cytokines in the serum. Intriguingly, infected ASC(-/-) mice also displayed reduced levels of IFN-α and IgM in the serum, indicating the overall protective role of ASC in restricting WNV infection. However, brains from ASC(-/-) mice displayed unrestrained inflammation including elevated levels of pro-inflammatory cytokines and chemokines such as IFNγ, CCL2 and CCL5, which correlated with more pronounced activation of the astrocytes, enhanced infiltration of peripheral immune cells in the CNS and increased neuronal cell death. Collectively, our data provides new insights into the role of ASC as an essential modulator of inflammasome-dependent and -independent immune response to effectively control WNV infection.
Links	PubMed Online version:10.1128/JVI.02667-12
Keywords
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:ASC		GO:0097202: activation of cysteine-type endopeptidase activity	ECO:0000315:		P		As seen in figure 1, ASC, a type of inflammasome adaptor protein, is essential for WNV-induced IL-1beta maturation and caspase 1 activation. This implies that ASC is a critical component of the WNV-induced inflammasome and that the production of IL-1beta is dependent on ASC.	complete CACAO 6903
MOUSE:ASC	involved_in	GO:0097202: activation of cysteine-type endopeptidase activity	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.