# Project 3:  Investigation of capsid-host factor interactions using minimal, soluble capsid lattice assemblies

> **NIH NIH P50** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $301,972

## Abstract

P3. Abstract
The mature HIV-1 capsid is an ordered protein shell that houses the viral genome and other viral or host
factors necessary for infection of a target cell. Its structure and stability are critical to infection—it must stay at
least partially assembled until it reaches the nuclear periphery, and a variety of host factors, either beneficial or
inhibitory to the virus, recognize specific capsid patterns only present in assembled cores. Potentially hundreds
of host factors bind the HIV-1 capsid, but our knowledge of host factor-capsid interactions at the molecular
level has been limited, in part caused by a lack of soluble capsid constructs that recapitulate lattice interfaces in
the assembled state and by challenges in purifying recombinant capsid-binding host factors. To overcome these
obstacles, we propose to design and build a repertoire of soluble capsid assemblies that represent all unique
capsid-lattice interfaces. This will be achieved by making use of previously published intra-hexamer
engineered disulfides and by incorporating the SpyCatcher/SpyTag system to create stable isopeptide bonds
between hexamers. With these new capsid assemblies in hand, we will use well-established biophysical and
biochemical techniques to map binding modes and determine high-resolution structures of these capsid
assemblies in complex with a range of host factors including TRIM5α, TRIMCyp, MxB, Fez1, and CypA, most of
which we have optimized for expression and purification. The proposed work will allow us to overcome major
experimental hurdles to advance mechanistic understandings of the capsid-related key steps of the HIV life
cycle.

## Key facts

- **NIH application ID:** 10219101
- **Project number:** 5P50AI150481-15
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Yong Xiong
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $301,972
- **Award type:** 5
- **Project period:** 2007-08-27 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219101

## Citation

> US National Institutes of Health, RePORTER application 10219101, Project 3:  Investigation of capsid-host factor interactions using minimal, soluble capsid lattice assemblies (5P50AI150481-15). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10219101. Licensed CC0.

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