# Core B: Biosafety Level 4 Core

> **NIH NIH P01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $215,591

## Abstract

BSL-4 CORE (Core B): PROJECT SUMMARY/ABSTRACT
The pathogenesis of Ebola virus (EBOV) disease is characterized by a dysregulated immune response
that includes the suppression of the innate immune system leading to “immune paralysis” and
paradoxically activation of inflammatory pathways characteristic of a “cytokine storm”. The goal of this
Program Project is to investigate the molecular mechanisms of the dysregulated immune response to
EBOV infections. EBOV infections must be performed under Biosafety Level 4/Animal Biosafety level
4 (BSL-4/ABSL-4) containment in accordance with government and institutional biosafety, biosecurity
and select agent regulations; therefore, this Program Project requires a BSL-4 Core (Core B). Core B
will use the BSL-4 and ABSL-4 facilities of the Galveston National Laboratory (GNL), which is part of
the University of Texas Medical Branch (UTMB). Interactions between Core B and the Research
Projects (RPs) will be coordinated by the Administrative Core (Core A).
Fundamental to the efforts included in the Program Project will be performing infections of primary
immune and nonimmune cells from deidentified human subjects with EBOV and a mutant with a
disabled interferon-inhibiting domain. Next, cells and tissues will be taken from rhesus macaques
infected with the same viruses, which will be used to complement in vitro data. The infected cells will
be used for investigation of transcriptional (Research Project [RP]1), posttranscriptional (RP2), and
posttranslational mechanisms (RP3) that lead to the dysregulated immune response to EBOV. The
initial steps of the experimental procedures, which involve infectious materials, for all RPs and targeting
of critical nodes leading to dysregulated responses at gene expression levels in vitro will be performed
in GNL BSL-4 facilities. The in vivo validation of the targeting will be performed in mice and rhesus
macaques will be performed in GNL ABSL-4 facilities.
The procedures that will be performed in Core B are critical for achieving the major goals of the
proposed studies, including: (a) detailed knowledge of transcriptional mechanisms leading to the
dysregulated immune response to EBOV, (b) elucidation of the role of posttranscriptional mechanisms
in the dysregulated immune response to EBOV, (c) elucidation of the role of posttranslational
mechanisms in the dysregulated immune response to EBOV, and (d) building and experimental
validation of a comprehensive model for the pathogenesis of EBOV infection and other severe viral
infections, such as Marburg, Lassa fever, dengue, and COVID-19. Completion of Core B Specific Aims
will provide critical support for RP1, RP2, and RP3 to identify the role of transcriptional,
posttranscriptional, and posttranslational mechanisms in the dysregulated immune response to EBOV.

## Key facts

- **NIH application ID:** 10188756
- **Project number:** 1P01AI150585-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Alexander Bukreyev
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $215,591
- **Award type:** 1
- **Project period:** 2021-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10188756

## Citation

> US National Institutes of Health, RePORTER application 10188756, Core B: Biosafety Level 4 Core (1P01AI150585-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10188756. Licensed CC0.

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