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Virus Details


VHFID10133

Host Factor Information

Pathogen Information

Publication Information

Host Factor Information

Gene Name IL-6
HF Protein Name Interleukin-6
HF Function
Uniprot ID P05231
Protein Sequence View Fasta Sequence
NCBI Gene ID 3569
Host Factor (HF) Name in Paper IL-6
Gene synonyms IFNB2
Ensemble Gene ID ENSG00000136244
Ensemble Transcript ENST00000258743.10;ENST00000404625.5
KEGG ID Go to KEGG Database
Gene Ontology ID(s) GO:0001781, GO:0002314, GO:0002384, GO:0002446, GO:0002548, GO:0002639, GO:0002675, GO:0002690, GO:0005125, GO:0005138, GO:0005576, GO:0005615, GO:0005788, GO:0005896, GO:0006953, GO:0006954, GO:0006959, GO:0007259, GO:0008083, GO:0008284, GO:0008285, GO:0010573, GO:0010574, GO:0010575, GO:0010628, GO:0010718, GO:0010888, GO:0014823, GO:0019221, GO:0030168, GO:0031018, GO:0031175, GO:0032494, GO:0032682, GO:0032722, GO:0032731, GO:0032733, GO:0032740, GO:0032745, GO:0032755, GO:0032757, GO:0032760, GO:0032966, GO:0033138, GO:0035633, GO:0042102, GO:0042593, GO:0042802, GO:0043065, GO:0043066, GO:0043410, GO:0045599, GO:0045669, GO:0045727, GO:0045765, GO:0045779, GO:0045893, GO:0045944, GO:0046427, GO:0048661, GO:0050731, GO:0050768, GO:0050796, GO:0050829, GO:0050830, GO:0050871, GO:0051091, GO:0051384, GO:0051607, GO:0060252, GO:0061470, GO:0061888, GO:0070050, GO:0070091, GO:0070092, GO:0070102, GO:0070301, GO:0071222, GO:0072540, GO:0072574, GO:0090091, GO:0090594, GO:0097421, GO:0097696, GO:0098586, GO:0150077, GO:0150078, GO:1900017, GO:1901731, GO:1902512, GO:1902895, GO:1903978, GO:1904894, GO:1904996, GO:2000553, GO:2000635, GO:2000660, GO:2000676,
MINT ID N.A.
STRING Click to see interaction map
GWAS Analysis Click to see gwas analysis
OMIM ID 147620;148000;604302
PANTHER ID PTHR48494;PTHR48494:SF1
PDB ID(s) 1ALU, 1IL6, 1P9M, 2IL6, 4CNI, 4J4L, 4NI7, 4NI9, 4O9H, 4ZS7, 5FUC, 7NXZ, 8D82, 8QY5, 8QY6,
pfam ID PF00489,
Drug Bank ID DB05767, DB05513, DB05744, DB12140, DB10770, DB10772, DB01404, DB13127, DB09221, DB09036, DB05470, DB05017,
ChEMBL ID CHEMBL1795129
Organism Homo sapiens (Human)

Pathogen Information

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

Publication Information

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 17
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