# Genome Structure, Transcription and Packaging of dsRNA Viruses

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $31,788

## Abstract

PROJECT SUMMARY/ABSTRACT
Double-stranded RNA (dsRNA) viruses comprise a large group of non-enveloped viruses characterized by
their ability to transcribe their RNA within an intact capsid (i.e., endogenous RNA transcription), thus evading
cellular antiviral responses to dsRNA. Among them, members of the Reoviridae family of dsRNA viruses are of
significance in both public health and basic science, exemplified respectively by the gastroenteritis-causing
rotavirus which is responsible for approximately half a million child deaths annually worldwide and the insect-
killing cytoplasmic polyhedrosis virus (CPV) which was used historically as a model in the discovery of RNA
capping. We have studied non-enveloped dsRNA viruses with single-layered (CPV), double-layered
[mammalian reovirus (MRV) and aquareovirus (ARV)], and triple-layered [rhesus rotavirus (RRV), Bluetongue
virus (BTV)] capsid. These viruses could also be classified based on the presence (such as CPV and
reoviruses) or absence (such as BTV and RRV) of an mRNA-capping turret on the icosahedral vertices of their
innermost shell. Results from the prior funding cycles have uncovered that BTV and CPV both use surface
trimers bearing similarities to fusion proteins of enveloped viruses (e.g., flu, AIDS and COVID-19 viruses) for
cell entry. We have also captured the asymmetrically attached transcriptional enzyme complex (TEC) at the
quiescent, initiation and transcribing stages of CPV, BTV and RRV; and identified both conserved and diverse
features among their structures and organizations of TEC and RNA capping. Our studies showed that, upon
cell entry, these viruses sense different environmental cues for internal transcription activation; and in the case
of CPV, sensing of SAM and ATP by the RNA-capping turret triggers a cascade of events: opening of the turret
iris, detachment of the trimeric spike, and initiation of endogenous transcription.
 The need to conserve endogenous RNA transcription and the structural diversities uncovered in our prior
studies have led to our overall hypothesis: genomes of dsRNA viruses have diverged substantially to allow
incorporation of RNA segments encoding the distinct proteins required to interact with different host cells,
giving rise to different genome and TEC organizations and variations to both RNA unwinding during
transcription and RNA capping during release. The goal of this renewal application is to test this hypothesis
with state-of-the-art cryogenic electron microscopy (cryoEM) and tomography (cryoET) by determining
representative dsRNA viruses’ genome organizations during quiescence, unwinding and capping during
transcription, and genome packing during assembly. We will model the genomes inside CPV, BTV, as well as
dsRNA viruses with one and two dsRNA segments for comparison (Aim 1). Capping and cap-snatching during
RNA transcription will then be investigated (Aim 2). Finally, we will visualize how different genomic RNA and
capsid proteins assemble t...

## Key facts

- **NIH application ID:** 10820018
- **Project number:** 3R01AI094386-11S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Z Hong ZHOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $31,788
- **Award type:** 3
- **Project period:** 2012-08-16 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10820018

## Citation

> US National Institutes of Health, RePORTER application 10820018, Genome Structure, Transcription and Packaging of dsRNA Viruses (3R01AI094386-11S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10820018. Licensed CC0.

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