Role of Class B Scavenger Receptors in Lipid Metabolism and Inflammation

Clinical Center

Investigators

Abstract

Regarding our research in lipid metabolism, we have demonstrated that SR-BI mediates LDL binding as well as cholesterol ester (CE) and triacylglycerol (TAG) sorting followed by their internalization to LDs. While about 60% of LDL- delivered neutral lipid (NL) to be uploaded to LDs requires neutral hydrolysis and de novo neutral lipid synthesis, about 40% is directly sorted and transported to LDs. Most importantly, both in vitro and in vivo data suggest that SR-BI is critical for short term LD formation from LDL in the liver and potentially other organs. Regarding our work in understanding APOBEC-3 regulation, we found that: 1) APOBEC3 induced HBV mutations occurred sequentially on HBV (-)-DNA from the reverse transcription start to termination site in parallel with the reverse transcription process;2) APOBEC3 mutation efficiency varied significantly with an order of A3B>>A3G>A3H-II or A3C with variation observed even with the same APOBEC3, suggesting the presence of other factors affecting APOBEC3 mutation activity; 3) Among APOBEC3s, A3B had a 3-fold higher mutation efficiency with up to 65% of cytidines being mutated, consistent with the kataegis-like A3B mutation signature in cancer. On the other hand, A3C had a unique higher mutation frequency on HBV genome populations with a preference for both 5TC and 5CC; and 4) APOBEC3 induced HBV mutation was detected in HBV rcDNA, not in cccDNA and pgRNA, suggesting that APOBEC3 induced mutation on HBV genomes occurs essentially as a singular event, occurring only within the nucleocapsid and involving rcDNA replication. We have begun to evaluate the role of class B scavenger receptors in the pathogenesis of SARS-CoV-2. We are evaluating the role of class B scavenger receptors in ApoL1 variant associated kidney diseases.