# The effects of influenza virus genomic heterogeneity on replication dynamics and the host response

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2022 · $384,904

## Abstract

Abstract
Defining the specific factors that govern the evolution and transmission of influenza A virus (IAV) populations
remains a critical open question in virology. IAV populations primarily consist of semi-infectious particles (SIPs)
that express highly heterogeneous incomplete subsets of viral genes, and thus depend upon complementation
through cellular co-infection to replicate. Viral genomic heterogeneity and co-infection dynamics likely play
enormous roles in determining the outcome of IAV infection, yet remain ill-defined. In the proposed studies, we
will utilize an array of novel single-virion and single-cell methods to define how genomic heterogeneity influences
both co-infection dynamics and the host response to infection. In our preliminary data, we reveal that IAV
superinfection, one of the primary mechanisms of viral co-infection, is regulated by the number of viral genes
expressed by an infecting virion, rather than the specific activity of the viral neuraminidase gene as has been
previously reported. As a consequence, superinfection is more frequent in viral populations that contain more
SIPs. In aim 1, we will dissect the specific molecular details of this unique viral gene dose-dependent mechanism
of superinfection regulation, as well as determine whether host intrinsic immune mechanisms are involved in
regulating superinfection. In aim 2, we will identify the specific viral genetic determinants that regulate
superinfection, and test whether IAV strains and mutants that differ in SIP production also vary in superinfection
potential as we predict. Finally, our aim 3 studies will build upon our preliminary data that identifies a distinct
cluster of host genes that is specifically regulated by the viral neuraminidase gene. We will use single cell
RNAseq to leverage the enormous amount of genomic heterogeneity present within IAV populations to dissect
the contributions of individual IAV gene segments in determining the overall host transcriptional response to
infection. Collectively, these studies will greatly expand our understanding of how genomic heterogeneity within
IAV populations shapes the replicative, evolutionary, and pathogenic potential of IAV populations.

## Key facts

- **NIH application ID:** 10468059
- **Project number:** 5R01AI139246-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Christopher Byron Brooke
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $384,904
- **Award type:** 5
- **Project period:** 2018-09-21 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468059

## Citation

> US National Institutes of Health, RePORTER application 10468059, The effects of influenza virus genomic heterogeneity on replication dynamics and the host response (5R01AI139246-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10468059. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*