Federal assistance awards · Assistance award

ROLE OF MYELOID CELL LRP1 IN RIFT VALLEY FEVER VIRUS INFECTION AND DISSEMINATION - PROJECT SUMMARY/ABSTRACT…

Federal financial assistance recorded from USAspending. This is not a procurement contract.

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ASST_NON_F32AI191453_075 · UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM… · Department of Health and Human Services

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Assistance award details

Assistance award identifier
ASST_NON_F32AI191453_075
FAIN
F32AI191453
Recipient
UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION
Awarding agency
Department of Health and Human Services
Funding agency
Department of Health and Human Services
Assistance listing (CFDA)
93.855
Total obligated
$85,540
Period
Sep 1, 2025 – Aug 31, 2026
Fiscal year
2025
Place of performance state
PA
Source file
FY2025_All_Assistance_Full_20261006.zip

Description

ROLE OF MYELOID CELL LRP1 IN RIFT VALLEY FEVER VIRUS INFECTION AND DISSEMINATION - PROJECT SUMMARY/ABSTRACT RIFT VALLEY FEVER VIRUS (RVFV) IS AN EMERGING ARBOVIRAL PATHOGEN THAT CAN CAUSE HEPATIC DISEASE, HEMORRHAGIC FEVER, OCULAR DISEASE, ENCEPHALITIS, AND TERATOGENIC EFFECTS. THIS VIRUS IS ENDEMIC IN AFRICA AND THE SAUDI ARABIAN PENINSULA AND COMPETENT MOSQUITO VECTORS ARE ALSO PRESENT IN THE AMERICAS. THE SIGNIFICANCE OF THIS VIRUS IS FURTHER EVIDENCED BY ITS STATUS AS AN NIAID CATEGORY A PATHOGEN AND INCLUSION ON THE WHO’S BLUEPRINT OF PRIORITY DISEASES. RVFV CAN INFECT MACROPHAGE AND DENDRITIC CELLS, AND IT IS HYPOTHESIZED THAT THIS IS THE MECHANISM BY WHICH RVFV DISSEMINATES THROUGHOUT THE BODY FOLLOWING A SUBCUTANEOUS INFECTION. YET, THIS HAS NOT YET BEEN VALIDATED IN VIVO. FOLLOWING A FOOTPAD INJECTION MIMICKING A MOSQUITO BITE, MOST INBRED MOUSE STRAINS SUCCUMB TO HEPATIC DISEASE 3 – 5 DAYS POST-INFECTION, WHICH HAS MADE THE STUDY OF RVFV DISSEMINATION DIFFICULT. LOW- DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN 1 (LRP1) WAS IDENTIFIED BY OUR LAB AS A HOST ENTRY FACTOR FOR RVFV. THIS PROTEIN IS EXPRESSED ACROSS SPECIES AND CELL TYPES PERMISSIVE TO RVFV. LRP1 IS AN IMPORTANT SIGNALING MOLECULE INVOLVED IMMUNE RESPONSES, BUT THE ROLE OF LRP1-MEDIATED SIGNALING DURING RVFV INFECTION IS UNKNOWN. THE DEVELOPMENT BY OUR LAB OF AN LRP1F/FALBCRE MODEL, WHICH RESULTS IN PROLONGED SURVIVAL PAST HEPATIC DISEASE, VALIDATES CELL SPECIFIC KO OF LRP1 AS A METHOD TO INVESTIGATE LRP1’S ROLE IN RVFV TROPISM AND ALLOWS FOR THE FURTHER STUDY OF RVFV DISSEMINATION WHICH WAS NOT PREVIOUSLY POSSIBLE. MACROPHAGES AND DENDRITIC CELLS EXPRESS LRP1, AND I HYPOTHESIZE THAT RVFV UTILIZES LRP1 TO ENTER AND INFECT THESE CELLS, DISSEMINATE THROUGHOUT THE BODY, AND INFECT VISCERAL ORGANS AND TISSUES. THE PROPOSED STUDIES AIM TO INVESTIGATE THE EXPRESSION LEVELS OF LRP1 ON MYELOID CELLS AND ASSOCIATE THIS EXPRESSION WITH SUSCEPTIBILITY TO RVFV. CRE/LOX KNOCKOUT MICE WILL BE UTILIZED T

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