# Harnessing cell-to-cell variability to understand viral infection outcomes

> **NIH NIH DP2** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $82,768

## Abstract

PROJECT SUMMARY / ABSTRACT
This is a DP2 NIAID New Innovators Award proposal to harness cell-to-cell variability to understand viral infection
outcomes at the single cell level. Infected cells differ in the outcome of infection (abortive/productive), the timing and
level of viral gene expression and the number of progeny they produce. Two striking phenomena revealed by studying
infection at the single cell level are (1) the ability of some cells to abort infection after viral gene expression has
commenced and (2) the fact most infected cells release very few progeny while a small fraction of cells release thousands
(here termed “super producers”). While it is now accepted that cell-to-cell variability affects infection outcome, we
currently lack a molecular understating of the determinants of infection outcome in single cells, mainly due to the lack of
appropriate tools and methodologies.
Understanding these determinants is likely to lead to the discovery of novel cellular anti-viral modalities, better design of
therapeutics and deepen our understanding of the viral life cycle. In this proposal I will apply cutting-edge technologies to
investigate virus-host interactions at the single cell level and gain mechanistic insights as to the host factors that control
the opposing phenotypes of abortive infection and super producers.
My central hypothesis, supported by my past work and preliminary data using Herpes Simplex virus 1 (HSV-1) as a model
system, is that infection outcome at the single cell level is dependent on the cell’s state at the time of infection and on the
activation of specific cellular transcriptional programs. To test this hypothesis I will develop new approaches to interrogate
virus-host interactions by combining viral genetics, single-cell RNA-sequencing, custom-made microfluidic devices, live-
cell imaging and machine learning approaches. My background in performing cross-disciplinary research through the
combination of classical virology, cell-biology, microfluidics and systems biology to study virus-host interactions uniquely
positions me to successfully tackle these important questions. My results will identify the host factors that determine
infection outcome and define a new paradigm, using cell-to-cell variability to understand virus-host interactions. The tools
and technologies will be developed using HSV-1 as a model system, and then applied to investigate other important viral
pathogens, in collaboration with leading virologists.
This “high-risk high-reward” project requires a considerable investment of time and resources and the construction of
new tools, making it a perfect fit for the DP2 program. The award will allow me to pursue cutting-edge science at the
interface of virology and single cell biology and establish a long-term research plan to decipher the cellular mechanisms
that control infection outcome.

## Key facts

- **NIH application ID:** 11079320
- **Project number:** 3DP2AI154437-03S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Nir Drayman
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $82,768
- **Award type:** 3
- **Project period:** 2022-08-18 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11079320

## Citation

> US National Institutes of Health, RePORTER application 11079320, Harnessing cell-to-cell variability to understand viral infection outcomes (3DP2AI154437-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11079320. Licensed CC0.

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