# Viral factors responsible for Lassa virus pathogenicity

> **NIH NIH R00** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2024 · $249,000

## Abstract

Lassa virus (LASV) is endemic in West African countries and causes outbreaks of LF annually. Although 
LASV is one of the most alarming pathogens from a public health perspective, there are few effective vaccines 
or therapeutics against LF. LASV must be handled at biosafety level 4 (BSL-4), due to its high pathogenicity. 
This is one of the largest barriers to the development of preventive or therapeutic approaches against LF. 
Furthermore, animal models of LF are limited, which is essential for basic research and development of 
countermeasures. Recently, we developed a novel guinea pig model of LF and found that LASV strain LF2384 
and LF2350 have completely different pathogenic phenotypes in guinea pigs. These two viruses have been 
isolated from human LF patients and pathogenicity of these viruses in guinea pigs is consistent with human 
cases. These unique combinations of immunocompetent rodent model and clinical isolated LASVs are strong 
tools, which allow us to reveal viral factors responsible for pathogenicity and molecular mechanisms 
underlying LASV pathogenicity. 
During K99 phase, we revealed that RNA-dependent RNA polymerase (L) is the determinant factor of 
pathogenic differences between LASV LF2384 and LF2350 by using the reverse genetic system and in vivo 
evaluation. While significant progress has been made in determining the pathogenic viral factor, much less is 
understood about the host response related to LASV pathogenesis. Therefore, in the proposed study, we will 
determine host factors responsible for LASV pathogenicity by using reverse genetics and in vivo experiments, 
and reveal novel molecular mechanisms of LASV L protein underlying LASV pathogenesis by using several 
in vitro molecular techniques. 
We will address this goal through three specific aims. In Specific Aim 1, we will reveal the pathophysiology of 
LASV infection in guinea pigs. In Specific Aim 2, we will determine the domain or amino acid residue(s) in L 
responsible for LASV pathogenicity by using reverse genetics and in vivo study. In Specific Aim 3, we will 
unveil molecular mechanisms underlying LASV pathogenicity. Taken together, we hope to address novel 
pathogenic mechanisms of LASV infection, leading to new insights to develop countermeasures against LF.

## Key facts

- **NIH application ID:** 10831563
- **Project number:** 5R00AI156012-04
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Junki Maruyama
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2021-08-05 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831563

## Citation

> US National Institutes of Health, RePORTER application 10831563, Viral factors responsible for Lassa virus pathogenicity (5R00AI156012-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10831563. Licensed CC0.

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