# Defining Arbovirus-Host Interactions Using a Novel Caenorhabditis elegans-based System

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $202,500

## Abstract

Project Summary
The transmission of arboviruses from insect hosts to animals and humans results in infections that range from
benign and self-limiting to fatal. However, the conserved immunological factors that restrict arbovirus replication
and pathogenesis in these diverse hosts are not well understood. We developed an in vivo model system using
the free-living nematode, Caenorhabditis elegans, to identify host factors that inhibit infection caused by vesicular
stomatitis virus (VSV), a model arbovirus. The inexpensive culture, genetic tractability, and small size of this
model organism make it a powerful and convenient system for investigating virus-host interactions. We
previously showed that VSV infection of C. elegans animals is ultimately lethal. Nevertheless, nematodes with
deficiencies in their antiviral RNA interference (RNAi) response exhibit elevated levels of VSV replication and
succumb to infection more rapidly. Therefore, it is evident that the RNAi response is a major antiviral defense
mechanism that minimizes viral replication and pathogenesis in C. elegans. However, it is unclear if nematodes
encode additional mechanisms to restrict arbovirus replication. Here we propose to use our VSV model to identify
conserved host factors that mediate resistance to infection in both nematodes and in humans. To discover host
factors that may interact with VSV, we conducted studies to identify nematode proteins that physically associate
with the VSV nucleocapsid (N) protein, the main structural component of the virus particle. We hypothesized that
some of these interacting proteins may be antiviral host factors that either target the VSV N protein or are
themselves inhibited by VSV N as part of a viral strategy to subvert host immune responses. Thus far, we have
identified four nematode factors with putative VSV N interactions that display antiviral properties in VSV
infections of adult nematodes. Importantly, our preliminary results indicate that these factors do not function in
the antiviral RNAi pathway, suggesting that they have independent mechanisms of restricting arbovirus infection.
Furthermore, we found the human counterparts (orthologs) of these nematode proteins to also exhibit antiviral
activities against VSV in human cell cultures. These results suggest that our unique approach may uncover
conserved facets of virus-host interplay. Our proposed studies have the following specific aims: 1) use the C.
elegans model to identify additional host factors that inhibit arbovirus replication; 2) determine if human orthologs
of the identified nematode factors also contribute to arbovirus restriction; and 3) develop tools for further
characterization of these virus-host interactions. Our long-term goal is to use this model system to define key
eukaryotic innate immune mechanisms that restrict arbovirus replication. Identifying such interactions may lead
to new strategies for the treatment of human arbovirus infections. This is particularly im...

## Key facts

- **NIH application ID:** 9844448
- **Project number:** 5R21AI144203-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Don Brad Gammon
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $202,500
- **Award type:** 5
- **Project period:** 2019-01-03 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9844448

## Citation

> US National Institutes of Health, RePORTER application 9844448, Defining Arbovirus-Host Interactions Using a Novel Caenorhabditis elegans-based System (5R21AI144203-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9844448. Licensed CC0.

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