# Determining the molecular mechanisms of HIV-1 maturation

> **NIH NIH R01** · UNIVERSITY OF DELAWARE · 2023 · $613,684

## Abstract

Project Abstract
Before a newly budded HIV-1 particle becomes fusogenic (and infective) it must undergo
maturation. During maturation the contents of the virion transform from a spherical shell into a
conical structure after a series of cleavages of the 55 kDa Gag polyprotein by the viral protease.
Proteolytic processing starts at the site between the spacer peptide 1 (SP1) and the
nucleocapsid (NC) and culminates in the separation of SP1 from the capsid protein (CA). The
initial cleavage event effectively separates the NC-gRNA layer from the viral membrane
inducing gRNA condensation. The last event activates a molecular switch that triggers a late
maturation event, namely the assembly of the mature HIV-1 capsid around the ribonucleic
protein. During maturation, the matrix protein (MA), that is embedded to the viral membrane via
a myristoyl group, is cleaved from CA, resulting in reordering of the MA lattice and alteration of
the composition of the lipid membrane. Although several structures of immature and mature CA
and MA hexamers have been solved by sub tomogram averaging, the molecular mechanism
connecting the multiple events that occur during HIV-1 maturation are still unclear. Here, we
propose to utilize full-scale molecular dynamics simulations, integrating shaped-based coarse-
grained and atomistic methods, to determine motion-structures that reveal the mechanistic
details of HIV-1 virion maturation. Results from the simulations will inform the engineering of
protein mutants for structural analysis and guide the experimental design of functional analyses
and testing of hypotheses derived from the molecular simulations.

## Key facts

- **NIH application ID:** 10750083
- **Project number:** 1R01AI178846-01
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** Juan Roberto Perilla Jimenez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $613,684
- **Award type:** 1
- **Project period:** 2023-08-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10750083

## Citation

> US National Institutes of Health, RePORTER application 10750083, Determining the molecular mechanisms of HIV-1 maturation (1R01AI178846-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10750083. Licensed CC0.

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