# Host dependence of influenza A virus reassortment

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $633,061

## Abstract

When two influenza A viruses (IAVs) co-infect the same cell, exchange of gene segments through
reassortment gives rise to up to 256 different viral variants. This process has the potential to bring together
viral genes that have evolved in distinct host species, which in turn can facilitate zoonotic transfer. In a host
infected with a single virus population, reassortment can furthermore couple beneficial mutations or purge
deleterious ones, thereby accelerating viral evolution. Using a unique experimental system that allows direct
quantification of reassortment, we have shown that this process of genetic exchange is highly efficient in cell
culture and in a guinea pig host. Indeed, the prevalence of reassortant viruses shed from co-infected guinea
pigs (up to 75%) suggests that reassortment is a routine feature of IAV infections in nature. IAVs circulate in a
wide range of avian and mammalian species, however, and it remains unclear whether our findings in guinea
pigs would extend to these natural hosts. We therefore propose to evaluate the efficiency of reassortment in
pigs, mallards, quail and chickens. Ferrets and guinea pigs will also be included as models of human IAV
infection. By comparing results among species we will not only gain important insight into the incidence of
reassortment in natural hosts, but also test the hypothesis that the efficiency of reassortment varies among
host species. To investigate the mechanisms determining IAV reassortment efficiency in vivo, we will use
immunohistochemistry to track the spread of co-infecting viruses over a time course after inoculation. We
hypothesize that reassortment is favored by focal spread within target tissues, creating local areas where cells
are infected at high multiplicity. Finally, since our work in cell culture has revealed that viral genomes lacking
one or more segments markedly enhance the frequency of reassortment, we will test whether the prevalence
of incomplete viral genomes varies with host species. Our preliminary data strongly suggest that missing
segments are lost, not during virion assembly, but rather after genomes are delivered to a new target cell. The
likelihood of segments reaching the site of replication furthermore appears to depend on the species from
which the target cell is derived. Thus, we propose that reassortment levels may be host dependent in part due
to differing frequencies of incomplete viral genomes and will test this novel concept through experimentation
both in cell culture and in animal models. Overall, the research proposed will deepen mechanistic
understanding of IAV reassortment, a critical process in the diversification, evolution and emergence of novel
influenza A viruses.

## Key facts

- **NIH application ID:** 9823845
- **Project number:** 5R01AI127799-04
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Anice C Lowen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $633,061
- **Award type:** 5
- **Project period:** 2016-12-05 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9823845

## Citation

> US National Institutes of Health, RePORTER application 9823845, Host dependence of influenza A virus reassortment (5R01AI127799-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9823845. Licensed CC0.

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