# HIV Release and Restriction

> **NIH NIH P50** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $611,507

## Abstract

ABSTRACT
This Project is designed to elucidate the mechanistic bases for HIV-1 budding and its inhibition by the host
factor retroCHMP3. To initiate budding, HIV-1 Gag binds ESCRT-I1-4 and ALIX5-7, two early-acting factors in the
host Endosomal Sorting Complexes Required for Transport (ESCRT) pathway. These factors, in turn, recruit
the late-acting ESCRT factors CHMP2, CHMP4 (ESCRT-III) and VPS4 (AAA ATPase)2,8-10 (reviewed in refs.
11-16). Numerous models for membrane constriction and fission have been proposed.17-26 We favor those in
which: 1) ESCRT-III proteins form spiraling filaments that recruit VPS4 and constrict the membrane neck from
the cytoplasmic face and 2) The VPS4 ATPase promotes lipid mixing by remodeling the underlying ESCRT-III
scaffold. We now propose to determine the structural bases for membrane remodeling by ESCRT-III filaments
and VPS4 (Aims 1 and 2), characterize how mammalian retroCHMP3 (ESCRT-III) proteins can inhibit HIV
budding without inducing cellular toxicity (Aim 3), and image ESCRT assemblies within budding virions by
electron cryotomography (Aim 4). These studies will reveal how HIV-1 uses the host ESCRT-III/VPS4
machinery to exit cells and how host retroCHMP3 proteins can specifically inhibit this process.

## Key facts

- **NIH application ID:** 9993255
- **Project number:** 5P50AI150464-14
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Adam Frost
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $611,507
- **Award type:** 5
- **Project period:** 2007-08-27 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9993255

## Citation

> US National Institutes of Health, RePORTER application 9993255, HIV Release and Restriction (5P50AI150464-14). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9993255. Licensed CC0.

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