# Examining the role of IP6 in HIV-1 replication

> **NIH NIH R21** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $228,144

## Abstract

Summary
It has been known for over 15 years that the in vitro assembly of HIV-1 particles can be stimulated
under particular conditions by the addition of inositol hexakisphosphate (IP6), but the mechanism and
biological relevance of this finding was never resolved. Recently, it was determined that IP6 binds to a
six-helix bundle that is formed by HIV-1 structural protein (Gag) and stimulates bundle formation. In
crystal structures, IP6 binds in the center of the six-helix bundle and forms a density that precisely
matches an unidentified density that had been reported in authentic HIV-1 particles. To explore the
importance of IP6 in HIV-1 replication, the Johnson lab generated two clonal knockout cell lines using
CRISPR that each lack a gene (IPPK and IPMK) required for the synthesis of IP6 in cells. These cell
lines both displayed a severe defect in their ability to produce infectious HIV-1 particles. However,
many questions remain about how IP6 affects HIV-1 replication.
The specific aims of this proposal are:
1. Determine what step in replication is inhibited in the IP6 deficient cells.
2. Quantitate the levels of IP6 in cells and virus, and determine the level required for HIV-1
replication.
3. Determine what retroviruses depend on IP6 for replication.
4. Determine if HIV-1 can adapt to IP6 deficient conditions.

## Key facts

- **NIH application ID:** 9852959
- **Project number:** 5R21AI143363-02
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Marc C Johnson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $228,144
- **Award type:** 5
- **Project period:** 2019-01-24 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852959

## Citation

> US National Institutes of Health, RePORTER application 9852959, Examining the role of IP6 in HIV-1 replication (5R21AI143363-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9852959. Licensed CC0.

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