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Principal Investigator: Amy Pate Patterson
Organization: CLINICAL CENTER
Fiscal Year: 2023
Funding agency: NIH Clinical Center
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.In a collaboration with NEI, we have published this year (PMID:37411618) that the low density lipoprotein receptor (LDLR) is involved with SARS-CoV-2 spike protein mediated uptake in ocular cells.
We are evaluating the role of class B scavenger receptors in ApoL1 variant associated kidney diseases.
Terms: <2019-nCoV S protein><2019-nCoV spike glycoprotein><2019-nCoV spike protein><APOL-I><APOL1><APOL1 gene><Affect><African Sleeping Sickness><African Trypanosomiasis><Apo-B><ApoB><Apolipoproteins><Apolipoproteins B><Atheroscleroses><Atherosclerosis><Atherosclerotic Cardiovascular Disease><Biology><Blood Vessels><Body Tissues><CD36><CD36 gene><COVID-19 S protein><COVID-19 spike glycoprotein><COVID-19 spike protein><COVID19 S protein><COVID19 spike glycoprotein><COVID19 spike protein><Cancers><Cardiovascular Diseases><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Cholesterol Esters><Cholesteryl Esters><Chronic><Clinical><Collaborations><Cytidine><Cytosine Ribonucleoside><Cytosine Riboside><DNA><Data><Defense Mechanisms><Deoxyribonucleic Acid><Development><Event><Family><Frequencies><GP3B><GP4><GPIV><Genetic Alteration><Genetic Change><Genetic defect><Genome><HBV><HDL><HDL Lipoproteins><Heavy Lipoproteins><Hepatitis B Virus><High Density Lipoproteins><High density lipoprotein><Homologous Serum Hepatitis Virus><Host Defense><Host Defense Mechanism><Human><Hydrolysis><Immunity><In Vitro><Induced DNA Alteration><Induced Mutation><Induced Sequence Alteration><Infection><Inflammation><Innate Immune Response><Innate Immune System><Innate Immunity><Integral Membrane Protein><Intermediary Metabolism><Intervention><Intervention Strategies><Intracellular Communication and Signaling><Intrinsic Membrane Protein><Investigation><Kidney><Kidney Diseases><Kidney Urinary System><LDL><LDL Lipoproteins><LDL Receptors><Link><Lipids><Lipoprotein Binding><Lipoprotein LDL Receptors><Lipoprotein Receptor><Lipoproteins><Liver><Low Density Lipoprotein Receptor><Low-Density Lipoproteins><Lytic><Malignant><Malignant - descriptor><Malignant Neoplasms><Malignant Tumor><Mediating><Messenger RNA><Metabolic Processes><Metabolic syndrome><Metabolism><Modern Man><Molecular><Mutate><Mutation><Native Immunity><Natural Immunity><Nephropathy><Non-Specific Immunity><Nonspecific Immunity><Nucleocapsid><Organ><Parasites><Pathologic><Pathway interactions><Pattern><Physiologic><Physiological><Play><Population><Protein Family><Proteins><Publishing><RNA Splicing><Receptor Protein><Regulation><Renal Disease><Research><Reverse Transcription><Rhodesian trypanosome><Risk><Role><SARS-CoV-2 S protein><SARS-CoV-2 pathogenesis><SARS-CoV-2 spike glycoprotein><SARS-CoV-2 spike protein><SARS-CoV2 S protein><SARS-CoV2 spike glycoprotein><SARS-CoV2 spike protein><SCARB3><SR-B proteins><Severe acute respiratory syndrome coronavirus 2 S protein><Severe acute respiratory syndrome coronavirus 2 spike glycoprotein><Severe acute respiratory syndrome coronavirus 2 spike protein><Signal Transduction><Signal Transduction Systems><Signaling><Site><Sorting><Splicing><T rhodesiense><T. rhodesiense><T.rhodesiense><Therapeutic><Tissues><Transcription Process><Transmembrane Protein><Transmembrane Protein Gene><Triacylglycerol><Triglycerides><Trypanosoma><Trypanosoma brucei rhodesiense><Trypanosoma rhodesiense><Trypanosome><Urd><Uridine><Variant><Variation><Viral Cancer><Viral Diseases><Virus Diseases><Work><alpha-Lipoproteins><atheromatosis><atherosclerotic disease><atherosclerotic vascular disease><beta-Lipoproteins><biological signal transduction><cardiovascular disorder><class B scavenger receptors><coronavirus disease 2019 S protein><coronavirus disease 2019 spike glycoprotein><coronavirus disease 2019 spike protein><developmental><fat metabolism><fatty acid transport><genome mutation><hepatic body system><hepatic organ system><in vivo><interventional strategy><kidney disorder><lipid metabolism><mRNA><malignancy><neoplasm/cancer><particle><pathogen><pathway><pgRNA><polypeptide><preference><prevent><preventing><prophylactic><protein function><psychological defense mechanism><receptor><renal><renal disorder><severe acute respiratory syndrome coronavirus 2 pathogenesis><sleeping sickness><social role><therapeutic target><uptake><vascular><viral infection><virus infection><virus-induced disease>