# In-depth study of antiviral RNA silencing in Caenorhabditis elegans

> **NIH NIH R01** · LOUISIANA STATE UNIV A&M COL BATON ROUGE · 2020 · $285,338

## Abstract

PROJECT SUMMARY
 Antiviral RNA silencing (AvRS), also referred to as antiviral RNA interference (RNAi), acts as
a major antiviral innate mechanism in fungi, plants, and invertebrates. Recent observations suggest that
AvRS is also active in undifferentiated mouse cells and appears to be essential for developing mouse
babies to fight against lethal viral pathogen. Virus destruction in AvRS is guided by small interfering
RNAs derived from viral double-stranded RNAs (dsRNAs), usually the replication intermediates.
Therefore, genetic mutations that accumulate in the viral genome during the term of virus replication
do not confer resistance to AvRS. Hence, mechanistic study of AvRS holds promise for developing
novel strategies for the treatment of viral infection caused human diseases.
 In mammals, interferon mediated antiviral immunity represents a major innate immunity against
viral infection. This antiviral immunity is often triggered upon the detection of invading viral RNAs by
three closely related RNA helicases termed RIG-I-like RNA helicases (RLHs). Among these three
RLHs, RIG-I and MDA5 detect virus-produced double-stranded RNAs (dsRNAs) in a sequence-
independent manner and, thus, are also resistant to genetic changes within the viral genome. Thus,
findings from the study of RLH mediated virus detection is also expected to facilitate the development
of novel antiviral therapies. Increasing evidence suggests that RIG-I also plays essential role in
regulating mammal development. Currently, it remains to be an open question how RIG-I regulates
development in mammals
 Viruses naturally infect and trigger AvRS in Caenorhabditis elegans, making C. elegans an ideal
model organism for the study of AvRS. Compared to other model organism, C. elegans has so far the
most, in terms of type species, genes identified as key components of AvRS. Because of its short life
span and genetic tractability, C. elegans also allows for rapid identification of novel AvRS genes for
in-depth study of AvRS. More importantly, accumulating evidence suggests that worm RLHs
contribute to both AvRS, by acting as a virus sensor, and worm development. Thus, C. elegans as a
model system would serve us well in addressing the question how the virus detection function of RLHs
is regulated and how RLHs contribute to the regulation of development.
 This application seeks to work on (1) genetic and functional characterization of the candidate
AvRS genes isolated from a random genetic screen; (2) mechanistic study of worm AvRS initiation;
(3) mechanistic study of viral transcript destruction by worm AvRS. Findings from the proposed
research are expected to not only improve our understanding of worm AvRS but also facilitate our
study on the regulation of RLH function in virus detection and the regulation of development by RIG-I
in mammals.

## Key facts

- **NIH application ID:** 9850600
- **Project number:** 5R01GM119012-04
- **Recipient organization:** LOUISIANA STATE UNIV A&M COL BATON ROUGE
- **Principal Investigator:** Rui Lu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $285,338
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850600

## Citation

> US National Institutes of Health, RePORTER application 9850600, In-depth study of antiviral RNA silencing in Caenorhabditis elegans (5R01GM119012-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9850600. Licensed CC0.

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