# Pilot project to elucidate the role of DDX60L in Ebola virus disease

> **NIH AI R03** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2026 · $183,875

## Abstract

SUMMARY
Preliminary Data, based on siRNA knockdown studies, suggests that host encoded DExD/H box family protein
DDX60L exerts anti-Ebola virus (EBOV) activity. We therefore hypothesize that DDX60L is a negative regulator
of EBOV replication that can influence EBOV disease (EVD). While constitutively expressed in a number of cell
types, DXX60L is an interferon (IFN) stimulated gene (ISG) and is related to DDX60, which is reported to
augment production of IFNα/β. Therefore, DDX60L may also contribute to the anti-EBOV effects of IFNs and
promote upregulation of IFN responses. As a negative regulator of infection, understanding the mechanisms of
DDX60L-mediated inhibition may suggest strategies to mitigate EVD. We proposed to define how DDX60L exerts
its anti-EBOV effects using a combination of siRNA knockdown and CRISPR-Cas9-based approaches. Studies
will be performed in cell lines that correspond to cell types infected by EBOV in vivo. These are the Huh7
(hepatocyte), A549 (epithelial) and THP-1 (monocyte/macrophage) cell lines. Because siRNA knockdown
measurably impairs EBOV growth in cell culture, we will use this approach to define effects on a transfection-
based EBOV replication cycle modeling system that can assay all the major steps in the virus replication cycle.
In parallel, we will use in knockdown studies a recombinant EBOV in which the viral VP30 coding sequences
have been replaced with GFP (EBOV-GFPΔVP30). This virus only replicates in cells that provide VP30 in trans,
and can be used at reduced biocontainment levels. Finally, we will assay the effects of knockdown in the context
of fully replication competent EBOV. For each system, we will perform assays in the absence and presence of
IFNα and define steps in the replication cycle affected by knockdown using a combination of approaches that
include measuring viral RNA synthesis, viral protein production and host IFNα/β responses. We will also build
additional experimental systems to further characterize

## Key facts

- **NIH application ID:** 11282275
- **Project number:** 1R03AI196368-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Christopher F Basler
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $183,875
- **Award type:** 1
- **Project period:** 2026-05-01T00:00:00 → 2027-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11282275

## Citation

> US National Institutes of Health, RePORTER application 11282275, Pilot project to elucidate the role of DDX60L in Ebola virus disease (1R03AI196368-01). Retrieved via AI Analytics 2026-06-30 from https://api.ai-analytics.org/grant/nih/11282275. Licensed CC0.

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