# Molecular Mechanisms of Viral Entry by Membrane Fusion

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2022 · $562,219

## Abstract

PROJECT SUMMARY
Membrane fusion, mediated by viral spike glycoproteins, is a key process in the infection cycle of all
enveloped human and animal viruses. The overall goal of this project is to understand the molecular
mechanisms of Ebola and human immunodeficiency virus entry by membrane fusion, by taking
combined state-of-the-art structural and cell biophysical imaging approaches. Although the crystal
structures of the ectodomains of several enveloped virus spike glycoproteins have been determined to
high resolution and although we and others have contributed NMR structures of the membrane-
interactive parts of some of these proteins over the years, we are only beginning to understand the
structural transformations that take place when these protein domains interact with membranes and
each other, and how these structures drive membrane fusion. In the previous grant period we have
made substantial progress towards elucidating the structures of the fusion loop, membrane proximal,
and transmembrane domains of the Ebola virus envelope glycoprotein and their pH-dependencies in
membrane environments. We have also discovered that HIV particles bind and fuse preferentially at
lipid discontinuities in plasma membranes of infected cells and that this process depends critically on
the level of membrane cholesterol. Building on these achievements, we now propose to (1) solve the
structure of the Ebola virus fusion loop in interaction with its membrane-proximal and transmembrane
domain, (2) determine the intracellular factors that trigger Ebola virus fusion in the late endosome, and
(3) determine the role of membrane heterogeneity in forming the fusion pore for HIV entry.

## Key facts

- **NIH application ID:** 10312785
- **Project number:** 5R01AI030557-30
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** LUKAS K TAMM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $562,219
- **Award type:** 5
- **Project period:** 1991-09-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10312785

## Citation

> US National Institutes of Health, RePORTER application 10312785, Molecular Mechanisms of Viral Entry by Membrane Fusion (5R01AI030557-30). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10312785. Licensed CC0.

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