# Probing the contribution of viral heterogeneity to interferon induction

> **NIH NIH K22** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $108,000

## Abstract

Project Summary
 Cell intrinsic innate immune pathways present a barrier that nearly all pathogens must overcome in
order to successfully complete their infectious lifecycle. Influenza A virus (IAV) is no different, and engages
several different strategies in order to evade or otherwise suppress recognition by the host. This is crucial to
viral survival, as the production of interferons, the central signaling molecules of the innate response, results in
the propagation of a highly antiviral state to which even IAV is susceptible. Regardless, IAV is still detected in a
small subset of infected cells. In order to understand, and potentially manipulate, the host response to IAV, we
must first understand the nature of those rare infections that propagate an interferon response. Does the
incredible genetic and behavioral diversity exhibited in IAV infections predispose their recognition? And, if so,
is there a single stereotyped pattern of immunostimulatory variation, or do multiple points of viral failure exist?
 Over the course of the two-year funding period, Dr. Russell will quantitatively measure how
heterogeneity in IAV populations impacts their recognition by innate immune pathways. This will require
sequencing bulk, infected, populations of cells as well as single-cell transcriptomic measurements – both of
which have been developed and piloted by Dr. Russell while in Dr. Jesse Bloom's lab. Moving beyond the
observational science enabled by these sequencing approaches, Dr. Russell will explore both newly- and
previously-identified immunostimulatory IAV variation to establish causality. This will include attempts to
ascertain whether all immunostimulatory variation acts through the same, shared, mechanisms. This will be
primarily accomplished by recapitulating variation in pure viral populations using a reverse-genetic approach,
permitting the independent exploration of individual sources of immunostimulatory heterogeneity. Lastly, Dr.
Russell will seek to expand his work beyond IAV to a related virus of human importance, Influenza B virus.
Comparisons across distinct viral lineages will provide vital insight into whether viral interactions with innate
immunity are static over evolutionary time, or whether they are relatively dynamic and thus intractable to a
generalizable therapeutic intervention. Overall, this work will generate a robust framework describing the
totality of innate immune recognition of these viruses, serving as a substantial resource to the field moving
forward.

## Key facts

- **NIH application ID:** 10073469
- **Project number:** 5K22AI141678-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Alistair B Russell
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $108,000
- **Award type:** 5
- **Project period:** 2019-12-20 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073469

## Citation

> US National Institutes of Health, RePORTER application 10073469, Probing the contribution of viral heterogeneity to interferon induction (5K22AI141678-02). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10073469. Licensed CC0.

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