datadragon
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NLRP3 inflammasome activation reactivates Epstein-Barr Virus. NLRP3 inflammasome inhibitors can efficiently repress EBV reactivation.
Epstein-Barr virus (EBV) is a highly prevalent human herpesvirus that persists for life in more than 95% of the adult population. The virus alternates between a latent phase and a lytic phase, both of which contribute to the initiation of the tumor process. Recent research has unveiled the involvement of components of the NLRP3 inflammasome in EBV reactivation, triggered by various stimuli. In the present work, we demonstrate that shikonin, a natural molecule with low toxicity which is known to inhibit NLRP3 inflammasome, can efficiently repress EBV reactivation. Similar results were obtained with apigenin and OLT 1177, two other NLRP3 inflammasome inhibitors. It is shown herein that shikonin repressed the transcription of reactivation-induced NLRP3 thereby inhibiting inflammasome activation and EBV lytic phase induction. https://www.sciencedirect.com/science/article/abs/pii/S0166354223001778
NLRP3 Inflammasome Activation in EBV Reactivation
Recent research has highlighted the pivotal role of NLRP3 inflammasome activation in the EBV productive cycle. During EBV reactivation in B lymphocytes, NLRP3 assembly and pro-caspase-1 activation occur. It is believed that caspase-1 subsequently degrades KAP1 (key heterochromatin regulator 1), a component of a silencing complex responsible for repressing various lytic phase genes, including BZLF-1.
Additionally, recent findings have shown that HMGB1 (High Mobility Group Box 1) cooperates with the NLRP3 inflammasome to sustain the expression of Zta, a crucial protein in EBV reactivation.
Shikonin's Inhibition of Epstein-Barr Virus Reactivation
Shikonin, with its well-documented anti-inflammatory properties, has been found to suppress NFκB and inhibit the formation of NLRP3 and AIM2 inflammasomes. These actions prevent caspase-1 activation, a critical step in the inflammatory response.
In the context of herpesvirus infections, several sensors can initiate inflammasome formation, such as IFI16, cGas (for viral DNAs), or RIG-I (for viral RNAs). In the case of EBV, it induces inflammasome activation through the recognition of viral DNAs (IFI16), EBER (RIG-I), or AIM2 in human monocytes.
Added notes: ER Stress activates the NLRP3 inflammasome which can lead to EBV reactivation among many other downstream effects. https://pubmed.ncbi.nlm.nih.gov/32447438/ https://pubmed.ncbi.nlm.nih.gov/31687078/ https://www.hindawi.com/journals/omcl/2019/3462530/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079978/
See also the previous posts this year by Violeta:
We show that this ubiquitous virus (Epstein−Barr virus) exploits assembly of the NLRP3 inflammasome to kick-start its lytic cascade.
The inflammasome may be activated by cell-intrinsic damage signals such as reactive oxygen species (ROS), lysosomal instability, and changes in intracellular electrolyte levels.
https://www.pnas.org/doi/10.1073/pnas.1919133117
Conclusion: Collectively, our results demonstrated for the first time that CB2R plays a protective role in EAE through promoting autophagy and inhibiting NLRP3 inflammasome activation.
Activating cannabinoid receptor 2 alleviates pathogenesis of experimental autoimmune encephalomyelitis via activation of autophagy and inhibiting NLRP3 inflammasome
https://pubmed.ncbi.nlm.nih.gov/25417929/
Epstein-Barr virus (EBV) is a highly prevalent human herpesvirus that persists for life in more than 95% of the adult population. The virus alternates between a latent phase and a lytic phase, both of which contribute to the initiation of the tumor process. Recent research has unveiled the involvement of components of the NLRP3 inflammasome in EBV reactivation, triggered by various stimuli. In the present work, we demonstrate that shikonin, a natural molecule with low toxicity which is known to inhibit NLRP3 inflammasome, can efficiently repress EBV reactivation. Similar results were obtained with apigenin and OLT 1177, two other NLRP3 inflammasome inhibitors. It is shown herein that shikonin repressed the transcription of reactivation-induced NLRP3 thereby inhibiting inflammasome activation and EBV lytic phase induction. https://www.sciencedirect.com/science/article/abs/pii/S0166354223001778
NLRP3 Inflammasome Activation in EBV Reactivation
Recent research has highlighted the pivotal role of NLRP3 inflammasome activation in the EBV productive cycle. During EBV reactivation in B lymphocytes, NLRP3 assembly and pro-caspase-1 activation occur. It is believed that caspase-1 subsequently degrades KAP1 (key heterochromatin regulator 1), a component of a silencing complex responsible for repressing various lytic phase genes, including BZLF-1.
Additionally, recent findings have shown that HMGB1 (High Mobility Group Box 1) cooperates with the NLRP3 inflammasome to sustain the expression of Zta, a crucial protein in EBV reactivation.
Shikonin's Inhibition of Epstein-Barr Virus Reactivation
Shikonin, with its well-documented anti-inflammatory properties, has been found to suppress NFκB and inhibit the formation of NLRP3 and AIM2 inflammasomes. These actions prevent caspase-1 activation, a critical step in the inflammatory response.
In the context of herpesvirus infections, several sensors can initiate inflammasome formation, such as IFI16, cGas (for viral DNAs), or RIG-I (for viral RNAs). In the case of EBV, it induces inflammasome activation through the recognition of viral DNAs (IFI16), EBER (RIG-I), or AIM2 in human monocytes.
Added notes: ER Stress activates the NLRP3 inflammasome which can lead to EBV reactivation among many other downstream effects. https://pubmed.ncbi.nlm.nih.gov/32447438/ https://pubmed.ncbi.nlm.nih.gov/31687078/ https://www.hindawi.com/journals/omcl/2019/3462530/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079978/
Endoplasmic reticulum stress causes EBV lytic replication
https://pubmed.ncbi.nlm.nih.gov/21849482/See also the previous posts this year by Violeta:
We show that this ubiquitous virus (Epstein−Barr virus) exploits assembly of the NLRP3 inflammasome to kick-start its lytic cascade.
The inflammasome may be activated by cell-intrinsic damage signals such as reactive oxygen species (ROS), lysosomal instability, and changes in intracellular electrolyte levels.
https://www.pnas.org/doi/10.1073/pnas.1919133117
Conclusion: Collectively, our results demonstrated for the first time that CB2R plays a protective role in EAE through promoting autophagy and inhibiting NLRP3 inflammasome activation.
Activating cannabinoid receptor 2 alleviates pathogenesis of experimental autoimmune encephalomyelitis via activation of autophagy and inhibiting NLRP3 inflammasome
https://pubmed.ncbi.nlm.nih.gov/25417929/
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