# Complete mapping of the functional and antigenic effects of mutations to Lassa virus glycoprotein

> **NIH NIH F30** · UNIVERSITY OF WASHINGTON · 2020 · $40,374

## Abstract

Project Summary/Abstract
 Despite many medical advances, viruses continue to cause significant human disease. Viral infections
are difficult to prevent or treat in large part due to the rapid evolution of viral entry proteins. Mutations in these
proteins can permit viruses to infect new hosts (including humans), better spread between hosts, and evade
immune responses and some therapeutics. The Bloom lab has developed high-throughput tools to completely
characterize the effects of all single amino-acid mutations to the viral entry proteins from influenza and HIV.
These tools have proven very powerful for better understanding how these viruses evolve and how they
escape from antibodies proposed for clinical use. However, current tools cannot be easily applied to other
viruses, including most emerging viruses.
 To better understand the effects of mutations to viral entry proteins from emerging viruses, I am
developing a general platform for the high-throughput characterization of mutations to viral entry proteins.
Based on a pseudotyped lentiviral system, this platform allows me to study the viral entry proteins from most
enveloped viruses. I will leverage this system, along with the high-throughput tools already developed in the
Bloom lab, to measure the effects of all amino-acid mutations to the viral entry proteins from emerging viruses.
 Specifically, I will use my platform to characterize the effects of mutations to the Lassa virus entry
protein from several strains of Lassa virus. Understanding the effects of mutations to the viral entry protein
from divergent lineages of Lassa virus will be important for determining how the diversity of this virus affects
the development of a broadly-protective treatment or vaccine. To further address the question of antibody
therapeutic development, I will completely characterize the ability of mutations to the Lassa virus entry protein
to mediate antibody escape from three human monoclonal antibodies currently undergoing therapeutic
development. These complete maps of antibody resistance will determine from which antibody it is most
difficult for the virus to escape and help evaluate and refine potential antibody immunotherapies.
 Overall, I will develop a general method to characterize the effects of mutations to viral entry proteins,
including those from emerging viruses. I will then leverage this approach to study the Lassa virus entry protein,
gaining actionable insight into Lassa virus entry protein function and antibody escape.

## Key facts

- **NIH application ID:** 9906444
- **Project number:** 1F30AI149928-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Katharine Holt Dusenbury Crawford
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,374
- **Award type:** 1
- **Project period:** 2020-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906444

## Citation

> US National Institutes of Health, RePORTER application 9906444, Complete mapping of the functional and antigenic effects of mutations to Lassa virus glycoprotein (1F30AI149928-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9906444. Licensed CC0.

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