# Role of the novel entry factor Lrp1 in in vivo tropism and pathogenesis of Rift Valley fever  virus

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $195,050

## Abstract

PROJECT SUMMARY/ABSTRACT
 The World Health Organization warns of a pending public health emergency caused by mosquito-borne
Rift Valley fever virus (RVFV). RVF is an important disease of domesticated livestock that is zoonotically
transmitted to people, where it causes a spectrum of illness from mild to lethal. The significance of RVFV is
highlighted by its designation as a NIAID Category A pathogen and its inclusion on the WHO's Blueprint of
Priority Diseases, emphasizing the potential impact of RVFV on the global health and economy. Little is known
about the entry factors that RVFV uses to infect cells from multiple species. Our rigorous and convincing
preliminary data identify a cell surface receptor in the host lipid metabolism pathway that mediates infection of
cells by RVFV. This proposal will determine the biological significance of this lipid receptor protein in RVFV
disease in mice through conditional knockouts in cell types that are relevant to RVFV infection, including
hepatocytes, neurons, and myeloid cells. We will use transient and genetic tissue-specific conditional gene
knockouts of the lipid receptor generated using the Cre/Lox system. We hypothesize that eliminating lipid
receptor expression in the liver will rescue mice from an otherwise highly lethal infection. We further hypothesize
that conditional and tissue-specific gene deletions of the lipid receptor in mice will limit RVFV-associated
pathogenic outcomes, including hepatic disease and encephalitis. Our highly collaborative and synergistic team
is led by Dr. Amy Hartman (PI), an expert in the pathogenesis of RVFV, and by Dr. Gaya Amarasinghe (Co-I), a
biochemist and biophysicist with expertise in host-pathogen interactions. This R21 proposal presents an
opportunity to expand upon our collaborative efforts to determine the biological relevance of the RVFV-lipid
receptor interaction in the mouse model. Completion of this proposal will have high impact on the field because
it is the first in vivo assessment of receptor usage by RVFV. All reagents are available including mouse strains,
viruses, and techniques; thus, the feasibility is high.

## Key facts

- **NIH application ID:** 10447151
- **Project number:** 5R21AI163603-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Amy L Hartman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $195,050
- **Award type:** 5
- **Project period:** 2021-07-07 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447151

## Citation

> US National Institutes of Health, RePORTER application 10447151, Role of the novel entry factor Lrp1 in in vivo tropism and pathogenesis of Rift Valley fever  virus (5R21AI163603-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10447151. Licensed CC0.

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