# Characterizing the role of LDL related receptor 1 (Lrp1) as host entry factor for multiple bunyaviruses

> **NIH AI R01** · WASHINGTON UNIVERSITY · 2026 · $767,375

## Abstract

Summary:
Bunyaviruses (Order: Bunyavirales) are a growing and diverse family of animal and human pathogens with 
pandemic potential. With over 300 members and an expanding distribution of mosquito and tick vectors, these 
viruses are responsible for increasing outbreaks of human disease and present a significant threat to human 
health. Rift Valley Fever virus (RVFV) is one of the well-studied bunyaviruses and is designated as an NIAID 
Category A pathogen and included in the WHO’s Blueprint of Priority Diseases. The Coalition for Epidemic 
Preparedness Innovations (CEPI) included RVFV as part of their emerging infectious diseases vaccine program, 
further emphasizing the potential impact on the global health and economy. Oropouche virus (OROV) is found 
in South America and has caused more than 30 large epidemics resulting in over 500,000 human cases, making 
it the second most common arboviral disease in South America behind Dengue fever. However, the true case 
number is likely much higher due to Oropouche fever being misdiagnosed as Chikungunya or Dengue. A third 
member, La Crosse virus (LACV) is found primarily in North America and is the primary cause of pediatric viral 
encephalitis in the United States. Neither OROV nor LACV have been as well studied as RVFV, and thus a 
significant gap remains in our broad understanding of bunyavirus pathogenesis. Currently there are no approved 
therapeutic drugs for treatment of RVFV, OROV, or LACV disease, further highlighting the need for our proposed 
studies. To address this need, we conducted a genomic screen that defined several critical factors, including 
Lrp1, an LDL family member. In support we provide compelling preliminary data including in vitro validation in 
Lrp1 sufficient and deficient cells, transcomplementation studies, and direct interaction between RVFV 
glycoprotein Gn in vitro. We also show that inhibition of Lrp1 by endogenous ligands in vitro in multiple cell lines 
from evolutionarily distinct h

## Key facts

- **NIH application ID:** 11311853
- **Project number:** 5R01AI169850-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Gaya K. Amarasinghe; Amy L Hartman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $767,375
- **Award type:** 5
- **Project period:** 2023-03-14T00:00:00 → 2028-02-29T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11311853

## Citation

> US National Institutes of Health, RePORTER application 11311853, Characterizing the role of LDL related receptor 1 (Lrp1) as host entry factor for multiple bunyaviruses (5R01AI169850-04). Retrieved via AI Analytics 2026-07-14 from https://api.ai-analytics.org/grant/nih/11311853. Licensed CC0.

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