# Assembly of Picornaviral Replication Complexes

> **NIH NIH R01** · COLORADO STATE UNIVERSITY · 2021 · $377,640

## Abstract

The picornaviruses are a family of small positive sense single stranded RNA viruses that cause a wide range
of diseases at an annual cost well into the hundreds of million dollars. Members include acute hepatitis A virus,
the heart disease causing coxsackie B3 virus, rhinoviruses that cause more than half the occurrences of the
common cold, and the paralyzing poliovirus. These viruses share a life cycle where RNA replication and viral
assembly occurs in large membrane anchored replication complexes assembled on the surfaces of vesicles
derived from the endoplasmic reticulum. The replication process is driven by a virally encoded RNA dependent
RNA polymerase (3Dpol) that is responsible for the synthesis of all viral RNA. This research project is focused
on the structure and assembly of the viral replication centers and on structure-function studies of the viral
polymerases to understand mechanisms that control of elongation rates and replication fidelity. We have
solved multiple crystal structures of 3Dpol as elongation complexes with bound RNA and these structures
revealed a novel mechanism by which RdRPs close their active sites for catalysis in response to nucleotide
binding. In this upcoming project period we will use biophysical and structural biology methods to further our
mechanistic understanding of RNA translocation by 3Dpol and to solve the structures of viral initiation and
uridylylation complexes. We will also use single molecule microscopy and particle tracking methods to directly
visualize the in vitro assembly of viral replication complexes onto supported lipid bilayers.

## Key facts

- **NIH application ID:** 10088366
- **Project number:** 5R01AI059130-15
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Olve Breien Peersen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $377,640
- **Award type:** 5
- **Project period:** 2004-04-01 → 2023-02-22

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10088366

## Citation

> US National Institutes of Health, RePORTER application 10088366, Assembly of Picornaviral Replication Complexes (5R01AI059130-15). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10088366. Licensed CC0.

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