# Hijacking host cellular motors for the nuclear entry of polyomaviruses

> **NIH NIH R00** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $248,879

## Abstract

Project Summary/Abstract
Polyomaviruses (PyVs) are small DNA tumor viruses that cause debilitating disease in humans, including the
often-fatal Merkel cell carcinoma by Merkel cell polyomavirus (MCPyV). To cause infection, these non-enveloped
viruses must transport through the crowded host cellular environment to reach the nucleus where transcription
and replication of the viral genome leads to lytic infection or cellular transformation. During entry, PyV, is
endocytosed and trafficked to the endoplasmic reticulum (ER) where it penetrates the ER membrane to reach
the cytosol. Once in the cytosol, the virus is disassembled and transported to the nucleus where it is thought to
enter the nucleus through the nuclear pore complex (NPC). How PyV reaches the nuclear membrane and is
subsequently imported into the nucleus have yet to be determined. Intracellular transport is mediated largely
through the actions of the kinesin and cytoplasmic dynein host motor proteins that transport cellular cargo
towards the periphery and center of the cell, respectively. Studies of the archetype PyV, simian virus 40 (SV40),
revealed that the virus exploits these motors in escaping the ER to reach the cytosol and for virus disassembly
in this compartment. This K99/R00 proposal seeks to understand the role of cellular motors in the subsequent
transport and nuclear entry of PyVs. During the mentored phase of this award, Dr. Spriggs will determine how
kinesin-1 and dynein coordinate the transport of disassembled SV40 to the host nucleus and the mechanism by
which it enters the nucleus through the NPC. At this time, she will receive training in high-resolution microscopy
techniques, including correlative light and electron microscopy (CLEM), that when used in combination with both
traditional and state-the-art biochemical approaches, will lead to impactful discoveries in viral and cellular nuclear
import mechanisms. While much of our knowledge of human PyV infection has come from the study of SV40,
key differences have been observed between it and MCPyV, the only PyV definitely associated with human
cancer. One prominent distinction lies in its proposed mechanism of nuclear entry, which may instead require
mitotic nuclear envelope breakdown. Despite its impact on public health, little is known of the basic biology of
MCPyV infection. During the independent phase, and with her K99 training, Dr. Spriggs will delineate the entry
pathway of this distinct human pathogen, culminating in a mechanistic understanding of its nuclear entry. When
combined with her strong background in virology and cell biology, learning high-resolution microscopy should
fully equip Dr. Spriggs to run a successful independent research program studying virus-host interactions.
Further, along with her highly motivated Advisory Committee, the University of Michigan provides an ideal
environment for her training, given its exceptional research facilities and professional development resources.

## Key facts

- **NIH application ID:** 10868562
- **Project number:** 5R00GM141365-05
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Chelsey Cierra Spriggs
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $248,879
- **Award type:** 5
- **Project period:** 2022-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10868562

## Citation

> US National Institutes of Health, RePORTER application 10868562, Hijacking host cellular motors for the nuclear entry of polyomaviruses (5R00GM141365-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10868562. Licensed CC0.

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