Within-host population dynamics and collective interactions of SARS-CoV-2 and influenza virus

Farjo, Mireille Noor

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https://hdl.handle.net/2142/132478 Copy

Description

Title

Within-host population dynamics and collective interactions of SARS-CoV-2 and influenza virus

Author(s)

Farjo, Mireille Noor

Issue Date

2025-11-10

Director of Research (if dissertation) or Advisor (if thesis)

Brooke, Christopher B

Doctoral Committee Chair(s)

Brooke, Christopher B

Committee Member(s)

• Kieffer, Collin
• Martinez, Pamela P
• Slauch, James M

Department of Study

Microbiology

Discipline

Microbiology

Degree Granting Institution

University of Illinois Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• virology
• sars-cov-2
• influenza

Abstract

Viral populations are comprised of an ever-diversifying assortment of individuals. This diversity can be observed from the global scale down to the most granular levels of infection, where genetically distinct viral genomes interact within a cell. Because every virus that circulates within a host population must initially emerge within a single individual, it is crucial to understand the factors that govern viral dynamics within a host. Intra-host viral populations are subject to evolutionary forces like selection and drift, as well as ecological processes arising from virus-virus interactions. These interactions can range from cooperation and antagonism, and they play a major role in shaping the composition of viral communities. To investigate the ways that these small-scale evolutionary and ecological forces influence broader patterns of viral circulation, we characterized how the within-host dynamics experienced by SARS-CoV-2 and influenza virus go on to shape the evolution of both viruses. Using longitudinal samples collected from a cohort of individuals infected with SARS-CoV-2, we described patterns of viral mutational diversity over the course of infection and across two different tissue sites. Variant dynamics were generally stochastic, revealing an important role for genetic drift during acute SARS-CoV-2 infections. However, we detected rare cases in which variants emerged to a high enough frequency for forward transmission. We also found that viral populations within certain individuals showed significant spatial structuring, with patterns of mutational diversity differing between nasal swab samples and saliva samples collected on the same day. This within-host spatial structure may be partially responsible for the highly stochastic variant dynamics we observed. We also used a combination of experimental and computational methods to characterize the role of superinfection exclusion in shaping influenza infections. As a mechanism of restricting coinfection, superinfection exclusion limits both genetic complementation and reassortment between influenza viruses, thereby restricting two major drivers of genetic and genomic diversity. We found that superinfection exclusion acted equally across different influenza strain pairs, regardless of the genetic distance between the two viruses, but that superinfection exclusion did not limit infection attempts from other RNA viruses — signifying that the mechanism of superinfection exclusion acts on a trait that is shared among influenza strains, but not necessarily across other viruses. Supporting this finding, we demonstrated how exclusion during secondary infection attempts appears to block the import of virions into the nucleus, a unique life history feature of influenza that is not shared among most other RNA viruses. Finally, we used a simulation method to define the fitness effects of coinfection across different genetic and environmental contexts, and found that coinfection frequently resulted in negative fitness consequences stemming from the masking of deleterious alleles and the generation of low-fitness reassortant genotypes, suggesting a potential adaptive logic behind the maintenance of superinfection exclusion. Taken together, our findings reveal how within-host infection patterns are shaped by genetic drift and competitive interactions between coinfecting viruses, restricting the degree of genetic diversity that is preserved at higher levels of infection.

Graduation Semester

2025-12

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/132478

Copyright and License Information

Copyright 2025 Mireille Farjo

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