# Deltaretrovirus Morphology and Particle Assembly

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2024 · $602,126

## Abstract

Project Summary/Abstract
The deltaretroviruses represent one of seven genera in the Retroviridae and are recognized as being complex
retroviruses that encode for gag, pol and env along with several important accessory genes. These viruses have
been associated with the development of lymphoid leukemias in humans (i.e., human T-cell leukemia virus,
HTLV) and cattle (i.e., bovine leukemia virus, BLV). Deltaretroviruses are notorious for being difficult to propagate
in cell culture, which has prohibited rigorous analyses of virus replication, including the steps involved in
retrovirus assembly. The detailed steps involved in retrovirus assembly are poorly understood even for the more
tractable systems, including human immunodeficiency virus (HIV). Our preliminary studies have revealed that
the deltaretroviruses have distinct immature and mature particle morphologies compared to other retroviruses,
as well as distinct Gag-Gag and capsid-capsid (CA-CA) lattice structures, which likely impacts virus particle
formation. Furthermore, we have made observations which reveal that HTLV Gag puncta biogenesis is distinct
among retroviruses, relying heavily on Gag recruitment to particle assembly sites by Gag already at the plasma
membrane. This distinctive pathway for particle assembly likely has important implications for establishment of
HTLV particle assembly sites and the dynamics of particle assembly. In this application, we propose to advance
our research in novel directions through innovative state-of-the-art experimental approaches, making use of
comparative retrovirology in order to provide deep insights into the nature of deltaretrovirus particle assembly
and maturation. In particular, we will apply cryo-electron microscopy/tomography (cryo-EM/ET), super-resolution
microscopy, total internal reflection fluorescence (TIRF) microscopy, and dual-color z-scan microscopy to
investigate the 1) structure-function analysis of deltaretrovirus maturation, 2) deltaretrovirus Gag recruitment and
puncta biogenesis, and 3) analysis of critical steps in deltaretrovirus particle biogenesis. The proposed studies
will extend our preliminary studies and exploit advanced imaging technologies to gain new insights into the
deltaretrovirus particle assembly pathway, which we have demonstrated as being distinct from other retroviruses.
This research will provide foundationally important knowledge regarding the details of virus assembly at the
plasma membrane for enveloped viruses.

## Key facts

- **NIH application ID:** 10826512
- **Project number:** 1R01GM151775-01A1
- **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:** $602,126
- **Award type:** 1
- **Project period:** 2024-07-15 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10826512

## Citation

> US National Institutes of Health, RePORTER application 10826512, Deltaretrovirus Morphology and Particle Assembly (1R01GM151775-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10826512. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*