# Research Project 2: Role of Posttranscriptional Regulatory Networks in the Pathogenesis of Ebola Virus Disease

> **NIH NIH P01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $358,439

## Abstract

RESEARCH PROJECT 2 (RP2): PROJECT SUMMARY/ABSTRACT
This overall Program Project seeks to address a significant knowledge gap concerning Ebola virus (EBOV): how
infection leads to a pathogenic rather than protective immune response. In this project, the focus is on how EBOV
infection alters posttranscriptional gene regulation in critical immune cell types and in cells that are heavily
infected (e.g., hepatocytes). There is limited understanding of how EBOV infection impacts host gene expression
at the posttranscriptional level. Indeed, although the importance of posttranscriptional regulation in gene
expression for multiple pathogenic human viruses is evident, this level of regulation has been understudied for
filoviruses.
The central hypothesis of Research Project 2 (RP2) is that cell type-specific and gene-specific posttranscriptional
responses in EBOV disease contribute to the maladaptive phenotypes of immune cells, eventually leading to
“immune paralysis” and hyperinflammation. To address this hypothesis, we will characterize the
posttranscriptional landscape during EBOV infections of primary human immune and nonimmune cells. We will
decipher the influence of EBOV infection on host RNA processing and translation. Massively parallel sequencing
approaches made possible by the Proteogenomics Core (Core C) will be used to define RNA processing
events, RNA modifications, and mRNA translation efficiency transcriptome-wide in naïve and infected cells.
Importantly, samples generated from the same experiments in the BSL-4 Core (Core B) will be used by all three
projects and thus we plan to compare our data with that of RP1 and RP3. Data analysis, integration, and
modelling will be performed in collaboration with the Bioinformatics and Modeling Core (Core D). These
experiments will yield new insights into the effect of EBOV infection on cellular gene expression in relevant cell
types. We will also characterize the posttranscriptional landscape during EBOV infection in vivo in nonhuman
primates. Using the data from these experiments, with Core D we will construct a comprehensive model of
regulated host pathways that modulate EBOV infection in different immune cell types. This model will identify
candidate genes that represent important nodes for these pathways and thus potential vulnerabilities for EBOV.
In collaboration with Core B, this project will validate posttranscriptionally altered genes and events, and ask
whether they are functionally important to cell-type specific responses to EBOV infection.
Completion of this project will reveal new and underappreciated layers of host responses to EBOV infection, and
provide a rich data resource for the field that will lead to new hypotheses to address the molecular basis for
EBOV pathogenesis. Moreover, we will identify critical new host and/or viral targets that can be exploited to
disrupt the pathogenicity of this deadly virus.

## Key facts

- **NIH application ID:** 10188760
- **Project number:** 1P01AI150585-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Mariano A. Garcia-Blanco
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $358,439
- **Award type:** 1
- **Project period:** 2021-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188760

## Citation

> US National Institutes of Health, RePORTER application 10188760, Research Project 2: Role of Posttranscriptional Regulatory Networks in the Pathogenesis of Ebola Virus Disease (1P01AI150585-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10188760. Licensed CC0.

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