Developing Novel Tools to Study Chemokine Receptor Ccr5 Expression and Function in Mice

PROJECT SUMMARY: CCR5 is a chemokine receptor that holds significant importance in public health due to the following factors: 1) CCR5 is the primary co-receptor for HIV infection; 2) approximately 1% of individuals with European ancestry worldwide possess a natural deficiency in CCR5; 3) an FDA-approved CCR5 antagonist exists for HIV treatment and is currently undergoing clinical trials for potential use in various chronic diseases. Our research has revealed that the absence of CCR5 leads to heightened vulnerability to West Nile virus (WNV), a neurotropic flavivirus, in both human subjects and mouse models. Additionally, we and other researchers have observed a similar susceptibility to other neurotropic pathogens, such as Japanese encephalitis virus, tick-borne encephalitis, cerebral malaria, and toxoplasma gondii. While these studies have been conducted using mice deficient in Ccr5, further in-depth investigations have been limited by the lack of appropriate tools for mouse experimentation. Through this proposal, our aim is to create a floxed Ccr5 reporter mouse and develop a collection of specific antibodies targeting Ccr5. These resources will facilitate research on CCR5's function, expression patterns, and its involvement in various inflammatory conditions and diseases.