# Structural Studies of Togaviruses

> **NIH NIH R01** · PURDUE UNIVERSITY · 2020 · $646,229

## Abstract

PROJECT SUMMARY
 Crystallography was the primary structural tool that first opened up structural investigation of
viruses at near-atomic resolution. For instance, the first near-atomic resolution structure of an animal
virus, namely a common cold virus, was determined by us in the mid-1980s using crystallographic
methods (Nature 317:145-153, 1985). However, larger viruses with lipid envelopes are too variable in
their structures and have too small a proportion of their surface involved in lattice contacts to make
well-ordered crystals. Cryo-electron microscopy has now emerged as the leading tool for advancing
structural biology. Single particle averaging of cryo-electron microscopic images is now frequently
approaching atomic resolution with the use of direct electron detection devices and technology to
compensate for blurring of images due to random motion during data acquisition. However, the limits
of this technology are becoming apparent in the investigations of progressively more complex
pleomorphic assemblies. Cryo-electron tomography has now emerged as an invaluable tool for the
determination of the structure of individual viral particles without reliance on the availability of identical
homogeneous particles. However, the resolution of tomographic reconstructions is usually insufficient
to determine structures in atomic detail. Thus, a small part of this grant application is dedicated
towards extending the resolution of tomographic maps.
 Alphaviruses and rubella virus constitute the Togavirus family because of their similarity in gene
order. Among alphaviruses, Chikungunya virus is a major world health concern because of its re-
emergence in Asia and Africa. We plan to extend our previous studies of the icosahedral, lipid-
containing alphaviruses, and tackle the more difficult structural analysis of the pleomorphic rubella
virus. Specifically, we are planning to obtain the structures of various alphaviruses when complexed
with host receptor molecules and with antibodies and small molecule inhibitors that block maturation,
attachment and fusion with host cells in order to study the structural intermediates encountered in the
viral life cycle. This information will provide viral targets that can be exploited for the design of specific
antiviral therapeutics. We are also developing new technology aimed at stretching and pulling
individual cryoEM images to make them more similar and homogenous to improve the resolution of
tomographic images of pleomorphic biological assemblies such as rubella virus.

## Key facts

- **NIH application ID:** 9849156
- **Project number:** 5R01AI095366-07
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Richard J. Kuhn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $646,229
- **Award type:** 5
- **Project period:** 2012-02-20 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849156

## Citation

> US National Institutes of Health, RePORTER application 9849156, Structural Studies of Togaviruses (5R01AI095366-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9849156. Licensed CC0.

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