Influenza viruses evolve rapidly, with major consequences for human health. In my PhD in Jesse Bloom’s lab at the University of Washington and Fred Hutchinson Cancer Research Center, I combined high-throughput sequencing technologies with basic evolutionary theory to characterize viral cooperation and influenza’s evolution within hosts.
For this work, I received the James F. Crow Early Career Researcher Award (2018) and the Harold M. Weintraub Graduate Student Award (2018), and I was a finalist for the Walter M. Fitch Award (2017). I was funded by the NSF Graduate Research fellowship (2014-2017) and a Fannie and John Hertz Foundation fellowship (2015-2019).
Within-host evolution of influenza viruses
Image credit: Kim Carney
How do influenza viruses evolve within hosts?
Influenza viruses evolve rapidly from year to year across the globe, with immense consequences for human health. This rapid global evolution begins with mutations that arise as viruses replicate within infected individuals, but little is known about how evolution within hosts compares to global evolution.
In my PhD, I deep-sequenced samples of influenza virus from immunocompromised patients with chronic infections that lasted multiple months (Xue et al., eLife 2017). We found that the same, small set of antigenic mutations arose independently in multiple patients and also reached high global frequencies. This work showed surprising similarities in influenza’s evolution across vastly different scales of space and time. Our work was also one of the first to show that chronic respiratory infections can accelerate viral evolution, a phenomenon that has now been seen for SARS-CoV-2 as well.
I also compared the evolutionary pressures that act on influenza virus within and between hosts during more typical, acute infections (Xue et al., Virus Evolution 2020). I showed that influenza’s genetic diversity in acute infections is dominated by transient, deleterious mutations, suggesting that selection for antigenic mutations occurs mostly when viruses transmit between hosts.
Read more about this work in The Atlantic, Wired, and Science News. I have also given a public lecture on my work at Seattle Town Hall.
Selected publications
Xue, K.S., Stevens-Ayers, T., Campbell, A.P., Englund, J.A., Pergam, S.A., Boeckh, M., Bloom, J.D. Parallel evolution of influenza across multiple spatiotemporal scales. eLife 6: e26875 (2017). DOI: 10.7554/eLife.26875
Xue, K.S., Bloom, J.D. Linking influenza virus evolution within and between human hosts. Virus Evolution 6(1): veaa010. (2020). DOI: 10.1093/ve/veaa010
Xue, K.S., Moncla, L.H., Bedford, T., Bloom, J.D. Within-host evolution of human influenza virus. Trends in Microbiol. 26(8):781-793(2018). DOI: 10.1016/j.tim.2018.02.007
Other publications
Xue, K.S., Bloom, J.D. Reconciling disparate estimates of viral genetic diversity during human influenza infections. Nature Genetics 51:1298-1301(2019). DOI: 10.1038/s41588-019-0349-3
Davis, A.K.F., McCormick, K., Gumina, M.E., Petrie, J.G., Martin, E.T., Xue, K.S., Bloom, J.D., Monto, A.S., Bushman, F.D., Hensley, S.E. Sera from individuals with narrowly focused influenza virus antibodies rapidly select viral escape mutations in ovo. J. Virol.:00859-18 (2018). DOI: 10.1128/JVI.00859-18
Viral cooperation
Image credit: Jacqueline Morgado
How do influenza viruses evolve within hosts?
RNA viruses like influenza mutate rapidly to form genetically diverse populations. My work has shown that two distinct influenza viral variants that differ by a single nucleotide mutation can cooperate in cell culture (Xue et al., eLife 2016). These two viral variants grow better together than they do apart, and viral populations grown in cell culture harbor a stable mixture of both viral variants. This cooperative interaction arises primarily in lab settings rather than in natural infections (Xue et al., mSphere 2017). This work provides one of the first specific, defined examples of viral cooperation.
Read more about this work from Hutch News.
Xue, K.S., Hooper, K.A., Ollodart, A.R., Dingens, A., Bloom, J.D. Cooperation between distinct viral variants promotes growth of H3N2 influenza in cell culture. eLife 5: e13974 (2016). DOI: 10.7554/eLife.13974
Xue, K.S., Greninger, A.L., Pérez-Osorio, A., Bloom, J.D. Cooperating H3N2 influenza virus variants are not detectable in primary clinical samples. mSphere 3: e00552-17 (2017). DOI: 10.1128/mSphereDirect.00552-17
Katherine Xue 