# HIV Gag lattice morphology and particle biogenesis

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $582,501

## Abstract

Abstract
A key aspect to antiretroviral target identification is understanding the nature molecular interactions, which
when perturbed, can result interfere with human immunodeficiency virus type 1 (HIV-1) replication. An
underexplored aspect of the HIV-1 replication cycle for discovery of novel antiviral targets has been the steps
involved in virus particle assembly. This is due, in part, to the relatively poor understanding of this phase of
virus replication – specifically as it relates to the behavior of Gag movement to the plasma membrane, the
engagement of particle budding sites, the molecular Gag-Gag interactions that create the immature Gag lattice,
and subsequent particle biogenesis. Detailed comparative analysis of close relatives can be highly informative
for the discovery of key antiretroviral targets for drug development. For instance, recent evidence indicates that
Gag-Gag interactions differ among retroviruses, which helps explain morphological differences among
immature retrovirus particles. Furthermore, we have made key preliminary observations of differences in the
pathways for Gag nucleation leading to punctum formation, as well as the nature of particle biogenesis also
remain poorly understood aspects of the retrovirus assembly pathway, particularly among human
immunodeficiency virus type 1 and its close relatives – i.e., human immunodeficiency virus type 2 (HIV-2) and
human T-cell leukemia virus type 1 (HTLV-1). In this application, we propose to investigate retrovirus
immature particle structure and particle biogenesis through innovative state-of-the-art experimental
approaches. In particular, we will apply cryo-electron microscopy/tomography (cryo-EM/ET), total internal
reflection fluorescence (TIRF) microscopy, photoactivated localization microscopy (PALM), and the novel
single-molecule technology of fluorescence fluctuation spectroscopy (FFS) in living cells to investigate 1)
comparative analysis of immature Gag lattice structures, 2) investigate the nature of human retrovirus particle
biogenesis, and 3) investigate the pathways for the nucleation of Gag oligomerization. These novel studies
harness innovative technologies in order to provide new insights into a highly significant and poorly understood
aspect of the HIV-1 life cycle and lead to the identification of antiretroviral targets for exploiting by intervention
using small molecules.

## Key facts

- **NIH application ID:** 9984960
- **Project number:** 5R01AI150468-04
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** JOACHIM D MUELLER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $582,501
- **Award type:** 5
- **Project period:** 2017-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984960

## Citation

> US National Institutes of Health, RePORTER application 9984960, HIV Gag lattice morphology and particle biogenesis (5R01AI150468-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9984960. Licensed CC0.

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