# Elucidating the molecular function of Kaposi's sarcoma-associated herpesvirus packaging accessory protein ORF68

> **NIH NIH F31** · YALE UNIVERSITY · 2024 · $33,980

## Abstract

Project Summary
The standard treatments against other human herpesviruses have limited efficacy against Kaposi’s sarcoma-
associated herpesvirus (KSHV). A mechanistic understanding of KSHV infection and virion production will help
us develop new therapies to limit spread of the virus and thereby prevent the associated diseases, such as
Kaposi’s sarcoma. Viral packaging is an essential, conserved process in herpesviruses and is therefore a
promising therapeutic target. Although the essential proteins and necessary molecular events of packaging are
known, we lack a detailed mechanistic understanding of the process. These knowledge gaps must be addressed
to enable rational drug design. ORF68 is an essential packaging protein of unknown function whose role in this
multi-step packaging process is unknown. Recombinant ORF68 forms a pentamer with a positively central
channel that binds dsDNA in vitro. This work will bridge a critical knowledge gap between these in vitro
observations and ORF68 molecular function during infection in vivo. In Aim 1, I will determine the oligomeric
state of ORF68 during KSHV infection in vivo. In Aim 2, I will determine if the ORF68 oligomerization interface
is required during KSHV infection in vivo. In Aim 3, I will directly assess whether DNA binds inside the ORF68
pentamer channel. This work will unveil the molecular function of ORF68 in the context of infection, bringing us
closer to a mechanistic model of KSHV packaging.

## Key facts

- **NIH application ID:** 10997774
- **Project number:** 1F31AI181429-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Sara Gelles-Watnick
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $33,980
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10997774

## Citation

> US National Institutes of Health, RePORTER application 10997774, Elucidating the molecular function of Kaposi's sarcoma-associated herpesvirus packaging accessory protein ORF68 (1F31AI181429-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10997774. Licensed CC0.

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