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Principal Investigator: Jean Kyou Lim
Organization: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Fiscal Year: 2024
Award: $84,500
Funding agency: National Institute of Allergy and Infectious Diseases
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.
Terms: <AIDS Virus><Abscission><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Amino Acids><Antibodies><Antigenic Determinants><Antigens><Assay><Autoregulation><Binding><Binding Determinants><Bioassay><Biological Assay><Biology><Blood Cells><Body Tissues><C-C CKR-5><C-C CKR-5 Gene><C-C Chemokine Receptor Type 5><C-C Chemokine Receptor Type 5 Gene><CC Chemokine Receptor 5><CC-CKR-5><CC-CKR-5 Gene><CC-CKR5><CCCKR5><CCCKR5 Gene><CCR-5><CCR-5 Gene><CCR5><CCR5 Protein><CCR5 Receptors><CCR5 gene><CD195 Antigen><CD195 Antigen Gene><CHEMR13><CHEMR13 Gene><CKR-5><CKR-5 Gene><CKR5><CKR5 Gene><CKR5 Receptors><CMKBR5><CMKBR5 Gene><CRE Recombinase><Cell Body><Cells><Cerebral Malaria><Chemokine (C-C Motif) Receptor 5><Chemokine (C-C) Receptor 5><Chemokine (C-C) Receptor 5 Gene><Chemokine Receptor Gene><Chemotactic Cytokines><Chronic Disease><Chronic Illness><Clinical Treatment Moab><Clinical Trials><Collection><Communities><Compensation><Data><Disease><Disorder><Egypt 101 virus><Enterobacteria phage P1 Cre recombinase><Epitopes><European><European ancestry><Evaluation><Excision><Exposure to><External Domain><Extirpation><Extracellular Domain><FDA approved><Flavivirus><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Frequencies><G Protein-Complex Receptor><G Protein-Coupled Receptor Genes><G-Protein-Coupled Receptors><GPCR><Gene Transcription><Generations><Genetic><Genetic Transcription><Group B Arbovirus><HIV><HIV Infections><HIV Receptors><HIV-1><HIV-1 Fusion Co-Receptor><HIV-1 Fusion Co-Receptor Gene><HIV-I><HIV1><HTLV-III Infections><HTLV-III Receptors><HTLV-III-LAV Infections><Hematopoietic><Homeostasis><Homologous Chemotactic Cytokines><Homozygote><Host Defense><Human><Human Immunodeficiency Virus Type 1><Human Immunodeficiency Viruses><Human T-Lymphotropic Virus Type III Infections><Human immunodeficiency virus 1><Hybridomas><Immunity><Immunize><Immunoblotting><Immunofluorescence><Immunofluorescence Immunologic><Individual><Infection><Inflammation><Inflammatory><Initiation Codon><Initiator Codon><Intercrines><Investigation><Investigators><Japanese B Encephalitis Virus><Japanese encephalitis virus><LAV-HTLV-III><Length><Leukocyte Trafficking><LoxP-flanked allele><Lymphadenopathy-Associated Virus><Mediating><Membrane><Messenger RNA><Mice><Mice Mammals><Modern Man><Molecular Interaction><Monoclonal Antibodies><Murine><Mus><N-terminal><NH2-terminal><Non-Polyadenylated RNA><Orthoflavivirus><Pathway interactions><Pattern><Peptides><Peripheral Blood Cell><Physiological Homeostasis><Predisposition><Proteins><Public Health><RNA><RNA Expression><RNA Gene Products><Reagent><Receptor Protein><Removal><Reporter><Research><Research Personnel><Research Resources><Researchers><Resources><Ribonucleic Acid><Role><SIS cytokines><Site><Specificity><Start Codon><Stop Codon><Surgical Removal><Susceptibility><System><T gondii><T. gondii><Termination Codon><Terminator Codon><Testing><Tick-Borne Encephalitis><Tick-Borne Encephalitis Virus><Tick-borne Viral Encephalitis><Tickborne Encephalitis Virus><Tissues><Toxoplasma gondii><Transcription><Translating><Translation Stop Signal><Virus-HIV><WNV><West Nile viral infection><West Nile virus><West Nile virus infection><Western Blotting><Western Immunoblotting><Wild Type Mouse><ZIKV><Zika Virus><aminoacid><antagonism><antagonist><bacteriophage P1 recombinase Cre><beta Actin><chemoattractant cytokine><chemokine><chemokine receptor><chronic disorder><cohort><combinatorial><extracellular><flow cytophotometry><floxed><floxed allele><hemopoietic><human subject><immunogen><infected with West Nile virus><infection with West Nile virus><innovate><innovation><innovative><insight><interest><lipid based nanoparticle><lipid nanoparticle><mAbs><mRNA><membrane structure><monoclonal Abs><mouse model><murine model><neuroprotection><neuroprotective><neurotropic><novel><pathogen><pathway><programs><protein blotting><receptor><resection><social role><tool><wildtype mouse><zikav><β-Actin>