# HIV particle morphology and biogenesis

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2024 · $715,974

## Abstract

Project Summary/Abstract
Understanding the nature of the molecular interactions involved in human immunodeficiency virus type 1 (HIV-
1) replication continues to provide important insights into the fundamental nature of retrovirus replication. Beyond
the importance of such basic science investigations in addressing crucial knowledge gaps in the field, such
studies can inform antiretroviral target identification, and have broad applications towards therapy and cure. One
of the key aspects of HIV-1 replication that has remained underexplored has been virus particle assembly. The
reasons for this have included the challenges associated with the detailed behavior of Gag translocation to the
plasma membrane, the engagement of particle assembly sites, the molecular interactions that drive virus particle
assembly, and subsequent particle biogenesis and morphology. Integrative, comparative retrovirology has been
particularly informative in gaining a deeper understanding of these steps in retroviral replication. For instance,
immature particle morphology and the flexibility of the immature Gag lattice differs among retroviruses, which
have been insightful for understanding the role of gaps in the Gag lattice and its relationship to relieving stress
of lattice curvature. Furthermore, the recruitment pathways for retroviral Gag punctum formation, as well as the
role and nature of the actin cortex on assembly site selection and biogenesis also remain poorly understood
aspects of the retrovirus assembly pathway. In this application, we propose to investigate comparative analysis
of HIV particle morphology and particle biogenesis through innovative state-of-the-art experimental approaches.
In particular, we propose to employ cryo-electron microscopy/tomography (cryo-EM/ET), total internal reflection
fluorescence (TIRF) microscopy, photoactivated localization microscopy (PALM), dual-color z-scan imaging and
double helix-point spread function (DH-PSF) imaging to perform 3D super-resolution imaging and 3D single
particle tracking in living cells to investigate 1) high-resolution comparative structural analysis HIV particle
morphology and maturation, 2) investigate Gag puncta biogenesis at particle assembly sites, and 3) investigate
the role of the actin cortex as a physical barrier in human retrovirus particle assembly. These novel studies
harness innovative technologies in order to provide new insights into a highly significant yet poorly understood
aspect of the HIV-1 life cycle, address important knowledge gaps in the field, provide insights into potential
targets for therapeutic intervention, and inform efforts toward next-generation HIV therapies.

## Key facts

- **NIH application ID:** 10884358
- **Project number:** 5R01AI177264-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** JOACHIM D MUELLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $715,974
- **Award type:** 5
- **Project period:** 2023-07-07 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884358

## Citation

> US National Institutes of Health, RePORTER application 10884358, HIV particle morphology and biogenesis (5R01AI177264-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10884358. Licensed CC0.

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