# Structural Virology of Tripartite Motif Proteins

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2021 · $327,459

## Abstract

Project Summary/Abstract
Virus components such as the HIV-1 capsid and virus-encoded RNA can trigger powerful innate defense
mechanisms when sensed by the host cell. Tripartite motif (TRIM) proteins are ubiquitin E3 ligases that
perform important roles in sensing these virus components: TRIM5a proteins are established to recognize the
incoming capsids of HIV-1 and retroviruses, and TRIM25 has an important but still enigmatic role in sensing
viral RNA. The principal goals of this R01 project are to elucidate the molecular mechanisms of these sensors.
In Aim 1, we propose to: (1) elucidate the molecular details of how TRIM5a recognizes HIV-1 and retroviral
capsids through an unprecedented mechanism of lattice-to-lattice pattern recognition, (2) understand how
multiple different protein-protein interactions in the TRIM5a/capsid complex cooperate to determine restriction
susceptibility, and (3) develop novel biochemical reconstitution methods to recapitulate and analyze TRIM5a-
mediated restriction in vitro. In Aim 2, we propose to: (1) elucidate the molecular details of how TRIM25
recognizes viral RNA, and (2) understand how this activity is coordinated with ubiquitination in order to enable
recognition of both viral genomes and virally-encoded messenger RNA. Insights from these studies are likely to
suggest novel ways to fight HIV-1 and other viral infections.

## Key facts

- **NIH application ID:** 10213609
- **Project number:** 5R01AI150479-08
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Owen Pornillos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $327,459
- **Award type:** 5
- **Project period:** 2014-09-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213609

## Citation

> US National Institutes of Health, RePORTER application 10213609, Structural Virology of Tripartite Motif Proteins (5R01AI150479-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10213609. Licensed CC0.

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