# Structure and function of the portal vertex on the herpes simplex virus capsid

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $642,666

## Abstract

ABSTRACT
This project aims to elucidate the interactions of the herpes simplex virus portal vertex with
replicated viral DNA and the HSV packaging machinery. The packaging and cleavage of
replicated viral DNA into preformed capsids is a critical step during herpesvirus infection. For
herpes simplex virus type 1 (HSV-1), this process requires the products of seven viral genes:
UL6, UL15, UL17, UL25, UL28, UL32, and UL33. Most of the proteins involved in capsid assembly
and DNA packaging are conserved suggesting that these mechanisms will also be similar for all
herpesviruses. The proposed research by the Homa and[CJF1] Conway laboratories combines
expertise in virology and structural biology for determining the interaction of the
cleavage/packaging proteins with the capsid portal vertex leading to stable packaging of a unit
length genome. Understanding the herpesvirus portal structure and its interaction with the
packaging machinery has been hampered due to the subtle morphological differences between
the portal and penton vertices. However, recent advances in cryoEM techniques have allowed
portals to be localized in images of intact capsids yielding important structural information about
the portal and associated proteins. The pUL6 portal dodecamer appears to be anchored to the
capsid by interactions with the peri-pentonal triplexes as well as helical density attributed to the
pUL17 and pUL25 subunits of the capsid vertex specific component (CVSC). Here we propose
combined biochemical and structural studies focusing on the unique portal vertex of wild type
HSV and packaging mutants that will provide insights into the mechanism of HSV genome
packaging. We aim to understand the functions of the CVSC components, their interactions with
the portal vertex and with the terminase complex in cleavage and retention of the packaged viral
genome. Based on published and preliminary studies, we believe the pUL17 is emerging as a key
player in capsid assembly and maturation. We hypothesize that pUL17 anchors the terminase
complex to the portal and, after packaging is complete, recruits pUL25 to the portal to retain the
viral genome. We will test the hypothesis in two specific Aims that together investigate the
structure and function of the portal vertex. Aim 1 focuses on the viral proteins required for the
portal complex to interact with the replicated viral genome and initiate the cleavage packaging
reaction. Aim 2 follows a complementary structural approach to understand the architecture of
the portal vertex, include the components required for different stages of assembly and
packaging. Our results will inform the development of innovative and specific therapeutics
designed to prevent herpesvirus replication by blocking DNA packaging.

## Key facts

- **NIH application ID:** 10235368
- **Project number:** 1R01AI154646-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** James F. Conway
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $642,666
- **Award type:** 1
- **Project period:** 2021-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10235368

## Citation

> US National Institutes of Health, RePORTER application 10235368, Structure and function of the portal vertex on the herpes simplex virus capsid (1R01AI154646-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10235368. Licensed CC0.

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