| Gene Name | MAPK |
| HF Protein Name | Mitogen-Activated Protein Kinase |
| HF Function | |
| Uniprot ID | O15264 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 5603 |
| Host Factor (HF) Name in Paper | MAPK |
| Gene synonyms | PRKM13 SAPK4 |
| Ensemble Gene ID | ENSG00000156711 |
| Ensemble Transcript | ENST00000211287.9 [O15264-1];ENST00000373766.9 [O15264-2] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0004674, GO:0004705, GO:0004707, GO:0005524, GO:0005634, GO:0005737, GO:0005829, GO:0006970, GO:0018105, GO:0032755, GO:0034644, GO:0035556, GO:0050729, GO:0051403, GO:0070301, GO:0071347, GO:0072709, GO:0072740, GO:0106310, GO:1903936, |
| MINT ID | O15264 |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 602899 |
| PANTHER ID | PTHR24055 |
| PDB ID(s) | 3COI, 4EYJ, 4EYM, 4MYG, 4YNO, 5EKN, 5EKO, 8X23, |
| pfam ID | PF00069, |
| Drug Bank ID | DB12010, DB05157, DB01017, |
| ChEMBL ID | CHEMBL2939 |
| Organism | Homo sapiens (Human) |
| Virus Name | Japanese encephalitis virus |
| Virus Short Name | JEV |
| Order | Amarillovirales |
| Virus Family | Flaviviridae |
| Virus Subfamily | N.A. |
| Genus | Flavivirus |
| Species | Japanese encephalitis virus |
| Host | Vertebrates |
| Cell Tropism | |
| Associated Disease | Encephalitis |
| Mode of Transmission | Sexual contact, blood, breast feeding |
| VIPR DB link | https://www.viprbrc.org/brc/vipr_search.do?species=Japanese_encephalitis_virus |
| ICTV DB link | https://ictv.global/report/183/flaviviridae |
| Virus Host DB link |
| Paper Title | Nucleotide-Binding Oligomerization Domain 1 (NOD1) Positively Regulates Neuroinflammation during Japanese Encephalitis Virus Infection |
| Author's Name | Zheng Chen 1, Zikai Zhao 2 3 4, Yixin Liu 2 3 4, Muhammad Imran 2 3 4, Jing Rao 2 3 4, Ning Cai 1, Jing Ye 2 3 4, Shengbo Cao 2 3 6 |
| Journal Name | MIICROBIOLOGY SPECTRUM |
| Pubmed ID | 35638852 |
| Abstract | Japanese encephalitis virus (JEV) is a neurotropic flavivirus that invades the central nervous system and causes neuroinflammation and extensive neuronal cell death. Nucleotide-binding oligomerization domain 1 (NOD1) is a type of pattern recognition receptor that plays a regulatory role in both bacterial and nonbacterial infections. However, the role of NOD1 in JEV-induced neuroinflammation remains undisclosed. In this study, we evaluated the effect of NOD1 activation on the progression of JEV-induced neuroinflammation using a human astrocytic cell line and NOD1 knockout mice. The results showed that JEV infection upregulated the mRNA and protein expression of NOD1, ultimately leading to an enhanced neuroinflammatory response in vivo and in vitro. Inhibition of NOD1 in cultured cells or mice significantly abrogated the inflammatory response triggered by JEV infection. Moreover, compared to the wild-type mice, the NOD1 knockout mice showed resistance to JEV infection. Mechanistically, the NOD1-mediated neuroinflammatory response was found to be associated with increased expression or activation/phosphorylation of downstream receptor-interacting protein 2 (RIPK2), mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), Jun N-terminal protein kinase (JNK), and NF-κB signaling molecules. Thus, NOD1 targeting could be a therapeutic approach to treat Japanese encephalitis. IMPORTANCE Neuroinflammation is the main pathological manifestation of Japanese encephalitis (JE) and the most important factor leading to morbidity and death in humans and animals infected by JEV. An in-depth understanding of the basic mechanisms of neuroinflammation will contribute to research on JE treatment. This study proved that JEV infection can activate the NOD1-RIPK2 signal cascade to induce neuroinflammation through the proven downstream MAPK, ERK, JNK, and NF-κB signal pathway. Thus, our study unveiled NOD1 as a potential target for therapeutic intervention for JE. |
| Used Model | U251.BV-2.BHK-23 |
| DOI | 10.1128/spectrum.02583-21 |
