# Analysis of human retrovirus particle assembly sites

> **NIH NIH F30** · UNIVERSITY OF MINNESOTA · 2022 · $55,052

## Abstract

Project Summary
Mucosal surfaces account for the vast majority of transmission events for human retroviruses – e.g., human
immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1). HIV-1 and HTLV-1
infection through the oral cavity represents a significant gateway for postnatal transmission from mother to child.
Virus spread via cell-to-cell transmission aids in establishment of viral infection in a newly infected individual.
While significant advancements in our understanding of retrovirus replication have been made, there are many
details that remain poorly understood. For instance, it is still unclear how virus particle assembly sites are
determined and how viral structural proteins and genetic material translocate to these locations on the inner
leaflet of the plasma membrane. The details of viral particle assembly are particularly unknown in the context of
cell-to-cell transmission. In this application, I propose to use molecular virology and state-of-the-art imaging
approaches to elucidate mechanisms of cell-to-cell transmission of different human retroviruses by comparative
analyses. It is well documented that HTLV-1 is efficiently transmitted via cell-cell contacts, i.e., the virological
synapse (VS). This is likely also the case for HIV-1 but has been commonly underappreciated. Virus transmission
at cell-cell contacts via the formation of a VS can result in polarized virus particle release into the VS. Virus
particle formation is driven by the Gag structural protein, which multimerizes at the virus assembly site (e.g.,
points of cell contact), resulting in particle biogenesis and release. In preliminary studies, our lab has observed
that the pool of Gag utilized in particle biogenesis in non-polarized cells was primarily recruited from the plasma
membrane for HTLV-1 whereas for HIV-1 Gag is recruited from the cytoplasm. This fundamental observation of
differential modes of Gag recruitment to particle assembly sites may help explain the distinct reliance of cell-to-
cell transmission as a productive mode of virus spread for HTLV-1 compared with that of HIV-1. I propose 2 lines
of investigation for this application. I will first investigate whether the differences in HIV-1 and HTLV-1 Gag puncta
biogenesis observed in non-polarized cells are also conserved in polarized cells. Second, I will investigate virus-
host cell interactions that help facilitate human retrovirus assembly, particularly in the context of cell-cell contacts,
which is of particular significance in oral biology. An important aspect of this aim will be the use of novel and
innovative technology, cryogenic-correlative light and electron microscopy (cryo-CLEM), in order to gain greater
insights into the role(s) of host cellular proteins important for virus assembly. Human retrovirus particle assembly
is a critical step in infectious virus transmission, including oral transmission at mucosal surfaces in the context
of cell-cell contacts. These stu...

## Key facts

- **NIH application ID:** 10485982
- **Project number:** 5F30DE031829-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Nora Willkomm
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $55,052
- **Award type:** 5
- **Project period:** 2021-09-27 → 2025-09-26

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10485982

## Citation

> US National Institutes of Health, RePORTER application 10485982, Analysis of human retrovirus particle assembly sites (5F30DE031829-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10485982. Licensed CC0.

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