摘要:
There is disclosed an assay system for determining therapeutic activity for treating restenosis, atherosclerosis, chronic rejection syndrome and graft versus host disease (GVHD) by measuring inhibition of cell migration activity in smooth muscle cells expressing a US28 receptor from the CMV genome. Specifically, there is disclosed a method for measuring inhibition of cell migration in isolated cells transfected with US28 or infected with CMV and stimulated with a ligand. There is further disclosed a method for treating atherosclerosis, restenosis, chronic rejection syndrome and graft versus host disease (GVHD), comprising administering an effective amount of an agent that is a US28 receptor antagonist, wherein a US28 receptor antagonist comprises an inhibitor compound that prevents transduction of US28 receptor signal stimulated by a US28 receptor ligand, wherein a US28 receptor ligand is selected from the group consisting of RANTES, MIP-1&agr; and MCP. The invention further provides a method for treating restenosis, atherosclerosis, chronic rejection syndrome and GVHD by administering KHSV encoded vMIP-2, fractalkine or herbimycin.
摘要:
Disclosed are small molecules capable of activating the type I interferon (IFN) response by way of the transcription factor IFN regulatory factor 3 (IRF3) were identified. A high throughput in vitro screen yielded 4-(2-chloro-6-fluorobenzyl)-N-(furan-2-ylmethyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (referred to herein as G10), which was found to trigger IRF3/IFN-associated transcription in human fibroblasts. To define cellular proteins essential to elicitation of the antiviral activity by the compound a reverse genetics approach that utilized genome editing via CRISPR/Cas9 technology was employed. This allowed the identification of IRF3, the IRF3-activating adaptor molecule STING, and the IFN-associated transcription factor STAT1 as required for observed gene induction and antiviral effects.
摘要:
The present invention provides methods of latent virus reactivation in monocyte-derived macrophages through allogeneic stimulation of peripheral blood mononuclear cells (“PBMC”), methods of culturing virus, and cultures of virally permissive monocyte-derived macrophages.