# Functional characterization of the enteroviral degradome

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $501,518

## Abstract

Project Summary
Enteroviruses are human pathogens that replicate in multiple organs and cause a variety of diseases,
including gastroenteritis, pneumonia, myocarditis, and encephalitis. Currently, little is known about how
enteroviruses alter the biology of infected cells. This proposed project, which is founded on our recent
publication documenting the cellular proteins that enteroviral proteases target for cleavage, will elucidate
the role of enteroviral proteases in changing the host cell enviornment during infection.
The initial investigations of a subset of cleavage targets have so far yielded two candidate proteins,
LSM14A and IRF2BP2, which activated innate immune signaling and inhibited viral replication in cultured
cells. Our mechanistic studies have begun to reveal the molecular details of how these proteins limit virus
infection and whether their innate immune functions are required for viral inhibition. These preliminary
findings have built the foundation to characterize other host targets and determine their ability to regulate
enterovirus infection.
We have established a toolkit of novel methodologies and reagents that will enable the proposed work.
For example, we have implemented an innovative experimental system that consists of human induced
pluripotent stem cell-derived mesenchyme-free intestinal epithelial cells, which are highly susceptible to
enteroviruses and respond to infection by triggering a robust innate immune program. Similarly, we have
generated human cell lines containing interferon-stimulated genes tagged at their endogenous loci with
fluorescent proteins, allowing real-time monitoring of immune induction in response to viral infections.
We will employ these and other tools to investigate the molecular details of how the host target LSM14A
activates innate immune signaling and inhibit viral infections (Aim 1); dissect the function of IRF2BP2 in
the enterovirus lifecycle (Aim 2); and generate a comprehensive list of functionally important target
proteins that have roles in enterovirus infection and/or antiviral innate immunity (Aim 3).
Completion of these aims will reveal host restriction factors against enteroviral replication as well as their
mechanisms of action. More broadly, this project will advance the understanding of enteroviral
pathogenesis and potentially inform the design of broadly acting preventive and therapeutic strategies
against enteroviral infections.

## Key facts

- **NIH application ID:** 10870016
- **Project number:** 5R01AI170877-03
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Mohsan Saeed
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $501,518
- **Award type:** 5
- **Project period:** 2022-07-07 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870016

## Citation

> US National Institutes of Health, RePORTER application 10870016, Functional characterization of the enteroviral degradome (5R01AI170877-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10870016. Licensed CC0.

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