# Under Pressure: Biophysical Mapping of Herpesvirus Capsid Assembly and Genome Packaging

> **NIH NIH DP2** · EMORY UNIVERSITY · 2023 · $1,367,863

## Abstract

Project Abstract
Herpesviruses are double-stranded-DNA viruses that infect most of the human population. These complex
viruses establish lifelong, dormant infections, periodically reactivating under certain conditions. Reactivation is
particularly detrimental to the immunocompromised, resulting in a variety of disease states, including blindness,
encephalitis, cancers, and death, yet there is no cure. There are nine types of human herpesviruses, classified
into three subfamilies, yet a vaccine is only available targeting one type. Furthermore, available antivirals are
suboptimal due to viral mutation. The lack of pan-herpesvirus therapeutics likely stems from the variations in
viral replication between subfamilies, yet certain aspects, such as the need for properly assembled capsids
containing genetic content, are conserved. Therefore, the long-term goal of this research is to formulate a
detailed mechanism as to how herpesviral capsids assemble and package DNA, both of which are essential for
all herpesviruses to replicate. Although great strides have been made over the years to understand these
processes, we still do not know how these dynamic and transient processes occur at the molecular level.
Therefore, the scientific premise of this work is to develop biophysical methodologies to monitor capsid
assembly and genome packaging in real-time. The work in this proposal capitalizes on an existing in-vitro capsid
assembly platform that we will use in conjunction with new technologies in light scattering and mass spectrometry
to understand how individual capsid proteins come together to form the capsid shell. Not only will this provide
missing information regarding this essential process but it will also create new methodologies for other
researchers studying large viruses. Additionally, work in this proposal will create a novel in-vitro herpesviral
capsid packaging assay, something that has yet to be done in the field. We will subject this assay to various
single-molecular approaches to understand how proteins involved in genome packaging, some with unknown or
incompletely defined roles, coordinate this process to achieve successful encapsidation. Together, these
innovative studies will not only provide fundamental knowledge regarding these essential processes but also
challenge existing paradigms, resulting in a more complete understanding of herpesviral replication that can be
exploited for preventative and therapeutic approaches.

## Key facts

- **NIH application ID:** 10685823
- **Project number:** 1DP2GM154151-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Elizabeth Bennett Draganova
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,367,863
- **Award type:** 1
- **Project period:** 2023-09-18 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10685823

## Citation

> US National Institutes of Health, RePORTER application 10685823, Under Pressure: Biophysical Mapping of Herpesvirus Capsid Assembly and Genome Packaging (1DP2GM154151-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10685823. Licensed CC0.

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