Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

European bat lyssaviruses (EBLV) types 1 and 2 are closely related to classical rabies virus (RABV), and are capable of causing rabies in terrestrial mammals, including humans. The authors have investigated the murine host innate immune response in the brain, salivary gland, spinal cord, and blood, following peripheral inoculation with EBLV-2. In the brain, increases in Toll-like receptor-3 (TLR-3) transcript preceded overt disease, with a range of inflammatory gene transcripts increasing during the clinical stage of infection. This included transcripts for interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and CXC chemokine ligand 10 (CXCL10). In the salivary gland, there was a small but significant increase of CXCL10 gene transcript and a limited increase in 2'-5' oligoadenylate synthetase (2'-5' OAS1) transcript. In the blood, there was an increase in levels of IFN-gamma and virus-neutralizing antibodies (VNAs) were detected prior to the appearance of clinical signs. These changes were associated with severe lymphocyte infiltration observed within the spinal cord and dorsal root ganglia (DRG), which was dominated by T lymphocytes and associated with widespread inflammatory changes. The authors speculate that the increase of inflammatory cytokines and chemokines in response to EBLV-2 infection leads to a dramatic increase in T-cell infiltration and provides evidence for a robust immune response to lyssavirus infection that may not commonly occur in RABV infection.
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PMID:Up-regulation of chemokine gene transcripts and T-cell infiltration into the central nervous system and dorsal root ganglia are characteristics of experimental European bat lyssavirus type 2 infection of mice. 1856 56

Many viruses target signal transducer and activator of transcription (STAT) 1 to antagonise antiviral interferon signalling, but targeting of STAT3, a pleiotropic molecule that mediates signalling by diverse cytokines, is poorly understood. Here, using lyssavirus infection, quantitative live cell imaging, innate immune signalling and protein interaction assays, and complementation/depletion of STAT expression, we show that STAT3 antagonism is conserved among P-proteins of diverse pathogenic lyssaviruses and correlates with pathogenesis. Importantly, P-protein targeting of STAT3 involves a highly selective mechanism whereby P-protein antagonises cytokine-activated STAT3-STAT1 heterodimers, but not STAT3 homodimers. RT-qPCR and reporter gene assays indicate that this results in specific modulation of interleukin-6-dependent pathways, effecting differential antagonism of target genes. These data provide novel insights into mechanisms by which viruses can modulate cellular function to support infection through discriminatory targeting of immune signalling complexes. The findings also highlight the potential application of selective interferon-antagonists as tools to delineate signalling by particular STAT complexes, significant not only to pathogen-host interactions but also cell physiology, development and cancer.
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PMID:Lyssavirus P-protein selectively targets STAT3-STAT1 heterodimers to modulate cytokine signalling. 3290 73