# Defining the Role of Host Factors in Ebola Virus RNA Synthesis

> **NIH NIH P01** · WASHINGTON UNIVERSITY · 2020 · $563,250

## Abstract

Program Director/Principal Investigator (Last, First, Middle): 
The overall goal of this Project is to identify cellular proteins that are required for Ebola virus replication. Ebola 
viruses pose significant risks to human health and national security. The 2014 outbreak in Western Africa 
infected more than 28,000 people and caused more than 11,000 deaths (per WHO statistics). Although 
vaccine candidates are showing promise in clinical trials, no clinically approved drugs are available and basic 
information about Ebola virus replication is lacking. Like all viruses, Ebola virus depends on cellular proteins 
for its replication. This dependence creates a potential “Achilles heel” that may be exploited to develop new 
approaches to treat Ebola virus infections. By studying Ebola virus-host cell interactions, we gain insight into 
the mechanisms of action of viral proteins and the strategies that the virus uses to interface with its host. 
However, relatively few host factors of Ebola virus replication have been reported and no systematic, genome- 
wide analyses have been performed. To address this gap, we will apply complementary technologies to 
develop high quality maps of Ebola virus-host cell interactions. In Aim 1 we perform a high content, genome- 
wide RNAi screen under BSL4 conditions with wildtype Ebola virus to identify novel host factors required for 
Ebola virus replication. The capacity to perform such a screen is unique to the research team. Since the host 
factors identified in the siRNA screen could act directly or indirectly to affect Ebola virus replication, in Aim 2 
we propose to identify cellular proteins that bind to Ebola virus replication proteins. Complementary protein- 
protein interaction discovery technologies (yeast two-hybrid assay and co-affinity purification plus mass 
spectrometry) are used to develop a more comprehensive Ebola virus-host cell protein interaction network than 
could be achieved with any single approach. Since the sequences of Ebola virus strains differ between 
outbreaks and the impact of these genetic changes on host cell interactions is not known, we systematically 
compare host cell binding partners of a 2014 outbreak strain to those of Ebola Zaire (1976). Host cell factors 
from Aims 1 and 2 are integrated with existing large-scale data sets in Aim 3 to develop strain-specific Ebola 
virus-host cell protein interaction networks. To create a more complete understanding of regulatory effects of 
the virus-host interactions, we will enrich the network in indirect transcriptional interactions using high- 
throughput RNA-seq profiling of a subset of host factors selected from Aims 1 and 2. Our research team is well 
qualified to accomplish the goals of this Project, having expertise in high-throughput screening of BSL4 
viruses, virus-host cell protein interactions, RNA-Seq profiling, and network-based bioinformatic analyses. Host 
factors will be tested for their effects on virus infection in Pro...

## Key facts

- **NIH application ID:** 9955177
- **Project number:** 5P01AI120943-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Douglas J. LaCount
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $563,250
- **Award type:** 5
- **Project period:** 2016-07-07 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9955177

## Citation

> US National Institutes of Health, RePORTER application 9955177, Defining the Role of Host Factors in Ebola Virus RNA Synthesis (5P01AI120943-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9955177. Licensed CC0.

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