Exploring the Therapeutic Potential of a Peptide Derived from a Poxviral Immune Evasion Protein
Poster Aug 04, 2014
Toll-like receptors (TLRs) have a role in viral detection leading to cytokine and IFN induction, and as such are targeted by viruses for immune evasion.
The poxviral protein A46 has been identified to inhibit TLR signalling by interacting with TIR domain containing proteins of the receptor complex to
collectively inhibit all TLR adaptor proteins that positively regulate transcription-factor activation. An inhibitory peptide derived from A46 termed VIPER
selectively targets TLR4. This research investigates what affect the polyarginine delivery sequence location has on VIPER activity in vitro. In this study,
9R-VIPER is shown to be more effective at TLR4 and TLR2 signal inhibition than VIPER for multiple signalling pathways. Novel mechanisms of TLR2-
driven interferon induction have been shown to be affected by 9R-VIPER and VIPER. The longevity of TLR4 inhibition by 9R-VIPER was shown to be
superior to VIPER. Residues required for peptide activity were identified. Structural information about 9R-VIPER and a loss-of-function mutant was
determined by NMR analysis.
Genome-wide association studies (GWAS) have identified more than 100 genetic loci associated with type 2 diabetes. The majority of these are located in the intergenic or intragenic regions suggesting that the implicated variants may alter chromatin conformation. This, in turn, is likely to influence the expression of nearby or more remotely located genes to alter beta cell function. At present, however, detailed molecular and functional analyses are still lacking for most of these variants. We recently analysed one of these loci and mapped five causal variants in an islet-specific enhancer cluster within the STARD10 gene locus. Here, we aimed to understand how these causal variants influence b-cell function by alteration of the chromatin structure of enhancer clusterREAD MORE
International Conference on Clinical Trials & Pharmacovigilance
Feb 28 - Mar 01, 2019