UC Merced

Inflammation occurs when chemokines are secreted at a site of injury or infection, mediating a buildup of immune cells. Therefore, inhibiting chemokines in some cases could be an appealing target to control inflammation. Many viruses have evolved strategies to subvert the human chemokine system by producing chemokine binding proteins. Among them, poxviruses encode vCCI (viral CC chemokine inhibitor), which has been shown to bind more than 20 CC chemokines with high affinity. Therefore, understanding the mechanism of the high binding affinity between vCCI and CC chemokines could pave a way to develop vCCI as a new therapeutic candidate to treat inflammation related disease. In collaboration with the Prof. Michael Colvin group, combining an experimental approach and computational methodology, to unveil the possible key residues in the function of interaction between vCCI and chemokines, our work shows vCCI Y80, E143, and I184 residues are important for its binding to a chemokine vMIP-II (vCCL2). The vCCI mutation Y80R showed a loss of binding of 55 fold compared to the wild type of protein in BLI experiments, while E143K, I184R mutants decreased binding affinity of 37 and 25 fold respectively. We also found some key residues (G17, V44, Q45) of TARC (CCL17) involved in the interaction with vCCI. Highest affinity was achieved with the triple mutant CCL17 G17R/V44K/Q45R, which gave a Kd of 0.25 ± 0.13 µM for the vCCI:CCL17 variant complex, a 68 fold improvement in affinity compared to the complex with wild type CCL17. Silk fibroin (SF or silk in abbreviation) derived from the species Bombyx mori has been recognized as a material for biomedical sutures for centuries. With excellent biocompatibility, biodegradability, and sufficient supply, silk fibroin has become a popular biomaterial in tissue engineering, drug delivery, and surgery. In addition, silk fibroin can be developed into a variety of shapes with multiple structures, such as 3D porous scaffolds, films, particulates, fibers, needle patches, etc. In this study, we investigated improving the adhesive property of SF scaffold to the wet tissue with the addition of polyethylene glycol (PEG) and glycerol, and realized the sustained release of an anti-HIV protein Griffithsin.