# HSV/VZV chimeric viruses for identifying critical virus herpesvirus assembly interactions

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2024 · $509,699

## Abstract

SUMMARY
Herpesvirus assembly is critically dependent on specific interactions between viral proteins. In nuclear
egress, the NEC heterodimer, consisting of pUL31 and pUL34, performs multiple functions and interacts
with multiple other viral factors. In many cases, however, the mechanistic consequence and significance of
those interactions is unknown. Similarly, cytoplasmic envelopment depends upon interactions made by a
few essential tegument proteins (VP16, pUL36 and pUL37 in HSV-1), but which of their interactions (other
than with each other) are important for this process is unknown despite a wide array of interaction partners
identified by proteomic and other approaches. Here we propose to use a novel directed evolution
approach for functional identification of crucial interactions. We replace an essential HSV gene with its
homolog from VZV and then perform a growth selection for viruses that can use the VZV homolog for
assembly. Mapping of the mutations that have occurred during this directed evolution can identify novel
functional interactions and establish the significance of others. We present preliminary data showing the
utility of this approach using a chimeric virus in which HSV-1 UL34 is replaced by VZV ORF24. We have
identified a novel functional interaction with HSV-1 ICP4 and validated the significance of a previously
reported interaction with ICP22. We propose to determine the mechanism of action of these critical
interactions and use the system to identify others. In addition, we propose to expand the use of this system
another gene target relevant to nuclear egress, pUL31.

## Key facts

- **NIH application ID:** 10763019
- **Project number:** 5R01AI150718-03
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** RICHARD J ROLLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $509,699
- **Award type:** 5
- **Project period:** 2022-02-01 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763019

## Citation

> US National Institutes of Health, RePORTER application 10763019, HSV/VZV chimeric viruses for identifying critical virus herpesvirus assembly interactions (5R01AI150718-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10763019. Licensed CC0.

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