# Translation Regulation by Enterovirus Proteinase

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $480,000

## Abstract

The long term goal of this research is to understand the mechanism by which enteroviruses
such as poliovirus (PV) and Coxsackievirus (CVB3) control cellular and viral translation in
infected cells and in turn, discern how translation and gene expression are regulated normally.
Translation regulation mechanisms now encompass translation silencing (e.g. microRNAs) and
dynamic assembly/disassembly of RNA granules, stress granules (SG) and P-bodies (PB) that
contain translationally-silenced mRNPs. These structures assist cell homeostasis during stress
and serve as temporary storage/triage sites for mRNPs, and in the case of PBs, sites for mRNA
decay. We discovered that PV and CVB3 destroys-disperses both SGs and PBs, the former by
cleavage of G3BP1, a key factor that nucleates formation of stress granules. Our emerging
evidence suggests stress responses are linked to innate immune responses at several levels to
form an integrated stress/innate immune response. In this funding period we discovered that
SGs are stress-activated platforms to signal innate immunity and that G3BP1 mediates
activation of PKR and NF-kB. We have also discovered that G3BP1 assembly of SGs is
mediated by reversible arginine methylation on G3BP1 and have linked methylation to functional
innate immunity output of SGs. In this proposal we will elucidate the role of protein arginine
methylation in innate immune activation as we have now found recruitment of a key methyl-
reader protein TDRD3 and several innate immune factors to SGs is dependent on methylation
state of G3BP1. We have found the methyl-reader TDRD3 is antiviral, Aim 2 will elucidate the
role of TDRD3 in recruitment and activation of innate immune factors in the absence of G3BP1
and the impact of its cleavage by virus protease. Aim 3 will determine molecular mechanisms of
activation of both PKR that is non-methylation dependent and NF-kB by G3BP1. This proposal
is innovative since the both the (i) role SGs as a signaling platforms in innate immunity and (ii)
the role of protein methylation in innate immune activation are novel. The proposed work is
significant since it is relevant to a broad range of DNA and RNA viruses that promote SG
formation and it promises to uncover unprecedented insights into novel protein-mRNP
interactions that link stress signaling to innate immune activation. This will open new conceptual
avenues for antiviral development.

## Key facts

- **NIH application ID:** 10216998
- **Project number:** 5R01AI050237-18
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Richard E Lloyd
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $480,000
- **Award type:** 5
- **Project period:** 2002-03-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216998

## Citation

> US National Institutes of Health, RePORTER application 10216998, Translation Regulation by Enterovirus Proteinase (5R01AI050237-18). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/10216998. Licensed CC0.

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