# Nuclear functions co-opted by human rhinovirus during replication in the cytoplasm of infected cells

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $465,684

## Abstract

Picornaviruses cause a wide range of significant human and animal diseases, including poliomyelitis, hepatitis,
encephalitis, myocarditis, and the common cold. Since they are among the most genetically simple of all RNA
viruses, members of the picornavirus family must usurp host cell functions and modify the cytoplasmic
environment to facilitate viral translation, RNA replication, and virion biogenesis. Among the many ways that
picornaviruses alter host cell functions is by re-localizing them from the nucleus to the cytoplasm where viral
replication takes place. The nuclear versus cytoplasmic separation of the major processes that lead to the
expression of protein-coding genes in eukaryotes requires a complex transport process that allows RNAs and
proteins to move between these two cellular compartments. The Picornaviridae family is one of several virus
families that disrupt the nucleo-cytoplasmic trafficking of cells to promote viral replication. Viral proliferation
requires the activity of host RNA-binding proteins that normally function in cellular gene expression and are
primarily localized to the nucleus. Picornaviruses alter nucleo-cytoplasmic trafficking to exploit these and other
nuclear proteins that are subsequently delivered to the cytoplasm to facilitate efficient viral replication. Our
recently-published analysis of the nuclear versus cytoplasmic proteome in human rhinovirus-infected cells has
established the identities of a large cohort of nuclear proteins that re-localize to the cytoplasm during infection.
In this application, state-of-the-art molecular and cell biology experiments are proposed to determine the
functional significance of this protein redistribution on human rhinovirus replication, focusing on nuclear RNA
binding proteins involved in mRNA splicing/processing and 3’ polyadenylation. A global analysis of protein
distribution during rhinovirus infection of different human lung cell lines by quantitative mass spectrometry is also
proposed to uncover novel virus-host interactions that may be respiratory cell-type specific. Results from these
studies should reveal novel mechanistic insights into how a respiratory virus like human rhinovirus co-opts
specific host nuclear functions and how these functions are altered or re-purposed for specific steps in viral
replication. Detailed knowledge of such interactions, particularly at essential interfaces between host proteins
and viral proteins and/or viral RNA sequences, promises to reveal new targets for antiviral therapies.

## Key facts

- **NIH application ID:** 10904007
- **Project number:** 5R01AI155962-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Paul D Gershon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $465,684
- **Award type:** 5
- **Project period:** 2021-07-02 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904007

## Citation

> US National Institutes of Health, RePORTER application 10904007, Nuclear functions co-opted by human rhinovirus during replication in the cytoplasm of infected cells (5R01AI155962-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10904007. Licensed CC0.

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