# Evolutionary insights into enterovirus tropism and pathogenesis

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $126,630

## Abstract

Project Summary
Virus infection is a dynamic process. Response to infection causes profound phenotypic changes within
infected and uninfected cells within the host. Simultaneous changes also occur in the viral population due to
within-host selection and evolution. The links between virus evolution, spread, and pathogenesis are complex,
but have profound effects on the development of viral disease. Recent advances in single-cell RNA
sequencing now allow the measurement of these dynamic cellular phenotypes and viral genotypes in complex
tissues with unprecedented detail. This proposed research is focused on the development and use of these
technologies to characterize virus evolution and host responses during enterovirus infection in an established
murine model of enterovirus pathogenesis.
Aim 1 focuses on the characterization of single-cell transcriptomes from healthy and infected mice to
characterize the host response to infection in complex tissues.
Aim 2 will use of emerging high-resolution deep sequencing approaches to characterize within-host viral
population dynamics within infected mice.
Aim 3 will explore the links between viral and host genotype to the kinetics of within-host spread and
pathogenesis of enteroviruses.
This work will quantify the evolutionary trajectories of infecting viral populations ​in vivo ​and correlate this with
cell- and tissue-specific gene expression responses to infection. In the mentored phase​, this work will focus
on the viral and host dynamics of poliovirus infection, and later, in the ​independent phase​, on the emerging
pathogenic enterovirus EV71. The proposed research and training goals will build on the strengths of the
candidate in systems biology and evolutionary biology, augmenting it with training in animal handling and
single-cell sequencing from infected animals. During completion of this award, Dr. Dolan will pursue his
transition to independence by participating in local seminars and international conferences, by advising
graduate students, and by conducting a search to identify and obtain an independent faculty position,
mentored by his career development committee. The result of the proposed aims will be a new paradigm for
future investigations of viral infection and pathogenesis.

## Key facts

- **NIH application ID:** 10000029
- **Project number:** 5K99AI139279-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Patrick Timothy Dolan
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $126,630
- **Award type:** 5
- **Project period:** 2019-08-21 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000029

## Citation

> US National Institutes of Health, RePORTER application 10000029, Evolutionary insights into enterovirus tropism and pathogenesis (5K99AI139279-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10000029. Licensed CC0.

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