# Conformational Dynamics and Functional Consequences of HIV Fusion at Lipid Phase Boundaries

> **NIH NIH R21** · GEORGIA INSTITUTE OF TECHNOLOGY · 2024 · $194,605

## Abstract

ABSTRACT
HIV infects cells via a process of membrane fusion, mediated by the envelope
glycoprotein. Fusion peptides from gp41 are inserted into host cell membranes as part of
this process. Prior work has shown that HIV fusion peptides localize to phase boundaries
in membranes and that HIV viral particles preferentially fuse at such boundaries. These
phase, or "raft", boundaries are controlled by cholesterol and are likely responsible for the
cholesterol-dependence of HIV entry. Here, we test what consequences phase
boundaries have for fusion peptide biochemistry and HIV entry. We hypothesize that viral
mutants lacking this phase-boundary property will have impaired membrane fusion and
will no longer depend on membrane cholesterol. We also hypothesize that partitioning to
phase boundaries controls the conformational plasticity of HIV fusion peptides. We test
both of these hypotheses by designing mutant fusion peptides using molecular dynamics
simulation and then testing their effects computational, biochemically, and in HIV entry
assays. Since membrane phase behavior is highly dependent on cell state, a biochemical
understanding of how HIV proteins interact with lipidic phases will also advance our
understanding of how cellular activation or lipid modulation can affect HIV entry.

## Key facts

- **NIH application ID:** 10924444
- **Project number:** 1R21AI179359-01A1
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Peter M Kasson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $194,605
- **Award type:** 1
- **Project period:** 2024-06-21 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10924444

## Citation

> US National Institutes of Health, RePORTER application 10924444, Conformational Dynamics and Functional Consequences of HIV Fusion at Lipid Phase Boundaries (1R21AI179359-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10924444. Licensed CC0.

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