# Retrovirus Structure and Assembly with Inositol Phosphates

> **NIH NIH R01** · EMORY UNIVERSITY · 2022 · $123,878

## Abstract

Project Summary
Assembly of Gag into an immature virus particle is a critical step in the viral life cycle. After
assembly the immature virus particle goes through a process called maturation which is
required to produce infectious virus particles. We recently showed that the small cellular
molecule, inositol hexakisphosphate (IP6) is required for both assembly and maturation, and
that decreasing IP6 levels in cells severely reduces the formation of infectious virus. While we
know have a “big picture” view of how IP6 affects HIV, there is still a great deal we don’t
understand. This proposal seeks to characterize the mechanism of IP6 induced immature
assembly, how IP6 promotes mature assembly, and if these assembly steps can be targeted by
antiretrovirals. Furthermore, preliminary work suggests that IP6 is a cofactor for other
retroviruses, and so this proposal will test the hypothesis that IP6 as a retroviral cofactor is
evolutionarily conserved. Specific Aim 1 is to further characterize how IP6 binds and promotes
HIV-1 assembly and maturation. High resolution cryo-EM analysis will be performed on IP6
assembled mature virus-like particles with and without cellular proteins that are known to bind to
the viral core in cells. The effect of maturation inhibitors Bevirimat and PF-46396, which bind to
the same region as IP6, on IP6 binding and enhanced assembly will be determined using a
series of biochemical assays. In addition, this aim will test the hypothesis that IP6 is utilized by
other lentiviruses. For example, preliminary data suggest that the Equine Infectious Anemia
Virus also employs IP6 for the production of infectious virus. Specific Aim 2 is to determine if
and how IP6 is utilized by retroviruses outside of the lentivirus genus. Preliminary data shows
that the alpha retrovirus Rous sarcoma virus (RSV), and the delta retrovirus Human T-Cell
Leukemia Virus (HTLV) both utilize IP6. We will identify the site of IP6 action on both viruses
using biochemical and structural approaches. We will also screen viruses from the other
retroviral genera to determine if they also utilize IP6. Specific Aim 3 is to determine if and how
IP6 related compounds affect HIV-1 immature assembly, maturation, and mature assembly.
Working with a collaborator, we will synthesize and screen IP6-like compounds in assembly and
maturation assays. This aim will help to determine if compounds that target the IP6 binding site
are a feasible antiretroviral strategy.

## Key facts

- **NIH application ID:** 10872754
- **Project number:** 7R01AI147890-05
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Robert A Dick
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $123,878
- **Award type:** 7
- **Project period:** 2019-08-05 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10872754

## Citation

> US National Institutes of Health, RePORTER application 10872754, Retrovirus Structure and Assembly with Inositol Phosphates (7R01AI147890-05). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10872754. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*