GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.
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. ' |
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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 |
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Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
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 | ||||
involved_in |
GO:0097202: activation of cysteine-type endopeptidase activity |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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