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About:
P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages
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schema:ScholarlyArticle
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wasabi.inria.fr
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Type:
Academic Article
research paper
schema:ScholarlyArticle
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type
Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
title
P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages
Creator
Suzu, Shinya
Chatterjee, Sanchari
Chattopadhyay, Soma
Chattopadhyay, Subhasis
Mahish, Chandan
Mamidi, Prabhudutta
Gama, Lucio
Nayak, Tapas
Sahoo, Subhransu
Subudhi, Bharat
Kumar Nayak, Tapas
Sanjai Kumar, P
source
Medline; PMC
abstract
Chikungunya virus (CHIKV), a mosquito-borne Alphavirus, is endemic in different parts of the globe. The host macrophages are identified as the major cellular reservoirs of CHIKV during infection and this virus triggers robust TNF production in the host macrophages, which might be a key mediator of virus induced inflammation. However, the molecular mechanism underneath TNF induction is not understood yet. Accordingly, the Raw264.7 cells, a mouse macrophage cell line, were infected with CHIKV to address the above-mentioned question. It was observed that CHIKV induces both p38 and JNK phosphorylation in macrophages in a time-dependent manner and p-p38 inhibitor, SB203580 is effective in reducing infection even at lower concentration as compared to the p-JNK inhibitor, SP600125. However, inhibition of p-p38 and p-JNK decreased CHIKV induced TNF production in the host macrophages. Moreover, CHIKV induced macrophage derived TNF was found to facilitate TCR driven T cell activation. Additionally, it was noticed that the expressions of key transcription factors involved mainly in antiviral responses (p-IRF3) and TNF production (p-c-jun) were induced significantly in the CHIKV infected macrophages as compared to the corresponding mock cells. Further, it was demonstrated that CHIKV mediated TNF production in the macrophages is dependent on p38 and JNK MAPK pathways linking p-c-jun transcription factor. Interestingly, it was found that CHIKV nsP2 interacts with both p-p38 and p-JNK MAPKs in the macrophages. This observation was supported by the in silico protein-protein docking analysis which illustrates the specific amino acids responsible for the nsP2-MAPKs interactions. A strong polar interaction was predicted between Thr-180 (within the phosphorylation lip) of p38 and Gln-273 of nsP2, whereas, no such polar interaction was predicted for the phosphorylation lip of JNK which indicates the differential roles of p-p38 and p-JNK during CHIKV infection in the host macrophages. In summary, for the first time it has been shown that CHIKV triggers robust TNF production in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and the interaction of viral protein, nsP2 with these MAPKs during infection. Hence, this information might shed light in rationale-based drug designing strategies toward a possible control measure of CHIKV infection in future.
has issue date
2019-04-12
(
xsd:dateTime
)
bibo:doi
10.3389/fimmu.2019.00786
bibo:pmid
31031770
has license
cc-by
sha1sum (hex)
196d55353760e8e1ddbc2e2cce92f806351b747c
schema:url
https://doi.org/10.3389/fimmu.2019.00786
resource representing a document's title
P38 and JNK Mitogen-Activated Protein Kinases Interact With Chikungunya Virus Non-structural Protein-2 and Regulate TNF Induction During Viral Infection in Macrophages
has PubMed Central identifier
PMC6473476
has PubMed identifier
31031770
schema:publication
Front Immunol
resource representing a document's body
covid:196d55353760e8e1ddbc2e2cce92f806351b747c#body_text
is
schema:about
of
named entity 'manner'
named entity 'molecular'
named entity 'parts'
named entity 'inflammation'
named entity 'production'
named entity 'responses'
named entity 'Infection'
named entity 'Protein'
named entity 'Mitogen-Activated'
named entity 'TNF'
named entity 'NON-'
named entity 'INTERACT'
named entity 'MOUSE MACROPHAGE'
named entity 'CELLULAR'
named entity 'MEDIATED'
named entity 'INVOLVED'
named entity 'ANTIVIRAL'
named entity 'INFECTION'
named entity 'SPECIFIC'
named entity 'HOST'
named entity 'TNF'
named entity 'STRONG'
named entity 'TIME'
named entity 'DECREASED'
named entity 'MIGHT BE'
named entity 'KEY'
named entity 'CHIKUNGUNYA VIRUS'
named entity 'LIP'
named entity 'PARTS'
named entity 'LOWER'
named entity 'QUESTION'
named entity 'JNK INHIBITOR'
named entity 'ADDRESS'
named entity 'THR-'
named entity 'UNDERNEATH'
named entity 'VIRUS'
named entity 'GLOBE'
named entity 'TRIGGERS'
named entity 'DIFFERENTIAL'
named entity 'PROTEIN-PROTEIN DOCKING'
named entity 'NSP2'
named entity 'CELLS'
named entity 'RESERVOIRS'
named entity 'INDUCTION'
named entity 'PATHWAYS'
named entity 'ROLES'
named entity 'INTERACTIONS'
named entity 'IN SILICO'
named entity 'MOSQUITO'
named entity 'MACROPHAGE'
named entity 'OBSERVED'
named entity 'INHIBITOR'
named entity 'CONCENTRATION'
named entity 'COMPARED'
named entity 'ANALYSIS'
named entity 'INDUCED'
named entity 'EXPRESSIONS'
named entity 'MAPKS'
named entity 'INDUCTION'
named entity 'ALPHAVIRUS'
named entity 'TRANSCRIPTION FACTORS'
named entity 'JNK'
named entity 'MACROPHAGE CELL LINE'
named entity 'TCR'
named entity '180'
named entity 'MEDIATOR'
named entity 'MACROPHAGES'
named entity 'BORNE'
named entity 'PREDICTED'
named entity 'FOUND'
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