| Gene Name | CD68 |
| HF Protein Name | N.A. |
| HF Function | |
| Uniprot ID | P34810 |
| Protein Sequence | View Fasta Sequence |
| NCBI Gene ID | 968 |
| Host Factor (HF) Name in Paper | CD68 |
| Gene synonyms | N.A. |
| Ensemble Gene ID | ENSG00000129226 |
| Ensemble Transcript | ENST00000250092.11 [P34810-1];ENST00000380498.10 [P34810-3] |
| KEGG ID | Go to KEGG Database |
| Gene Ontology ID(s) | GO:0002437, GO:0002605, GO:0005764, GO:0005765, GO:0005886, GO:0016020, GO:0031669, GO:0031902, GO:0035577, GO:0071222, GO:0072594, GO:0140052, |
| MINT ID | P34810 |
| STRING | Click to see interaction map |
| GWAS Analysis | Click to see gwas analysis |
| OMIM ID | 153634 |
| PANTHER ID | PTHR11506;PTHR11506:SF2 |
| PDB ID(s) | N.A., |
| pfam ID | PF01299, |
| Drug Bank ID | N.A., |
| ChEMBL ID | N.A. |
| 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 | Lack of Interferon (IFN) Regulatory Factor 8 Associated with Restricted IFN-γ Response Augmented Japanese Encephalitis Virus Replication in the Mouse Brain |
| Author's Name | Aarti Tripathi 1, Bhupendra Singh Rawat 2, Sankar Addya 3, Milan Surjit 1, Prafullakumar Tailor 2, Sudhanshu Vrati 4, Arup Banerjee 1 10 |
| Journal Name | JOURNAL OF VIROLOGY |
| Pubmed ID | 34379515 |
| Abstract | Interferon regulatory factor 8 (IRF8), a myeloid lineage transcription factor, emerges as an essential regulator for microglial activation. However, the precise role of IRF8 during Japanese encephalitis virus (JEV) infection in the brain remains elusive. Here, we report that JEV infection enhances IRF8 expression in the infected mouse brain. Comparative transcriptional profiling of whole-brain RNA analysis and validation by quantitative reverse transcription-PCR (qRT-PCR) reveals an impaired interferon gamma (IFN-γ) and related gene expression in Irf8 knockout (Irf8-/-)-infected mice. Further, Ifnγ knockout (Ifnγ-/-) mice exhibit a reduced level of Irf8. Both Ifnγ-/- and Irf8-/- mice exhibit significantly reduced levels of activated (CD11b+ CD45hi, CD11b+ CD45lo, Cd68, and CD86) and infiltrating immune cells (Ly6C+, CD4, and CD8) in the infected brain compared to those of wild-type (WT) mice. However, a higher level of granulocyte cell (Ly6G+) infiltration is evident in Irf8-/- mice as well as the increased concentration of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP1) levels in the brain. Interestingly, neither the Irf8-/- nor the Ifnγ-/- conferred protection against lethal JEV challenge to mice and exhibit augmentation in JEV replication in the brain. The gain of function of Irf8 by overexpressing functional IRF8 in an IRF8-deficient cell line attenuates viral replication and enhances IFN-γ production. Overall, we summarize that in the murine model of JEV encephalitis, IRF8 modulation affects JEV replication. We also show that lack of Irf8 affects immune cell abundance in circulation and the infected brain, leading to a reduction in IFN-γ level and increased viral load in the brain. IMPORTANCE Microglial cells, the resident macrophages in the brain, play a vital role in Japanese encephalitis virus (JEV) pathogenesis. The deregulated activity of microglia can be lethal for the brain. Therefore, it is crucial to understand the regulators that drive microglia phenotype changes and induce inflammation in the brain. Interferon regulatory factor 8 (IRF8) is a myeloid lineage transcription factor involved in microglial activation. However, the impact of IRF8 modulation on JEV replication remains elusive. Moreover, the pathways regulated by IRF8 to initiate and amplify pathological neuroinflammation are not well understood. Here, we demonstrated the effect of IRF8 modulation on JEV replication, microglial activation, and immune cells infiltration in the brain. |
| Used Model | BV2, N9, N2a, HAP1, HAP1 Irf85bp del |
| DOI | 10.1128/JVI.00406-21 |
