601 South Goodwin Avenue
Urbana, IL 61801
Host-Pathogen Interactions, Molecular Evolution, Molecular Immunology, Regulation of Gene Expression, Virology
Disease Research Interests
Understanding viral replication, pathogenesis, and evolution
Influenza virus remains a major global health concern, despite the decades-long existence of a licensed vaccine. This ongoing threat is a direct function of the virus’ remarkable adaptability, which enables it to transmit within and between widely divergent host species while deftly evading herd immunity. Unfortunately, we still know very little about the specific mechanisms that govern influenza virus transmission, pathogenesis, and evolution.
My laboratory is primarily focused on understanding how heterogeneity and collective interactions within virus populations influence broader patterns of viral evolution and infection outcomes. Influenza virus populations are enormously heterogeneous, and most viral particles carry a functionally incomplete set of gene segments and thus cannot replicate independently. Rather than serving as dead-end products, widespread co-infection in vivo allows these incomplete particles to replicate and exchange gene segments through complementation. Collective interactions between heterogeneous particles can have profound effects on the behavior of the population as a whole, and the outcome of infection. We and our collaborators are currently employing a wide range of approaches spanning molecular virology, cell biology, evolutionary biology, single cell microfluidics, bioinformatics, and mathematical modeling to better understand this crucial, under-explored area of virus biology.
We are also interested in understanding the genetics of influenza virus immune escape and transmission, with the overall goal of improving strategies for universal vaccination. The specific factors that govern the continual antigenic evolution of influenza virus within the human population remain poorly understood. We have developed improved methods for ultra-deep viral population sequencing that allow us to dissect the process of antigenic evolution within and transmit between hosts like never before.
Specific areas of study within the lab include:
- Defining how patterns of viral heterogeneity and collective interactions within viral populations influence their evolutionary and pathogenic potential.
- Understanding how cellular heterogeneity and stochastic patterns of antiviral immune induction shape the host response to infection.
- Defining the epistatic interactions between viral gene segments and determining how they influence viral evolution.
- Using single-particle/single-cell analysis to examine how the interplay between viral and host heterogeneity shapes infection outcome.
- Employing ultra-deep population sequencing methods to understand how influenza populations maintain fitness while evading host immunity.
B.A. (Biology), Washington University, 2003
Ph.D (Microbiology & Immunology), University of North Carolina, 2010
Postdoctoral (Viral Immunology), Laboratory of Viral Diseases, NIAID, 2010-2015
Additional Campus Affiliations
Smith RL, Gibson LL, Martinez PP, Ke R, Mirza A, Conte M, Gallagher N, Conte A, Wang L, Fredrickson R, Edmonson DC, Baughman ME, Chiu KK, Choi H, Jensen TW, Scardina KR, Bradley S, Gloss SL, Reinhart C, Yedetore J, Owens AN, Broach J, Barton B, Lazar P, Henness D, Young T, Dunnett A, Robinson ML, Mostafa HH, Pekosz A, Manabe YC, Heetderks WJ, McManus DD, and Brooke CB. 2021. Longitudinal assessment of diagnostic test performance over the course of acute SARS-CoV-2 infection. J. Infect. Dis. DOI: 10.1093/infdis/jiab337.
- Highlighted in NIH Director’s blog (https://directorsblog.nih.gov/2021/04/06/new-initiative-puts-at-home-co…)
Martin BE, Harris JD, Sun J, Koelle K, and Brooke CB. 2020. Cellular co-infection can modulate the efficiency of influenza A virus production and shape the interferon response. PLOS Pathogens. DOI: 10.1371/journal.ppat.1008974
Sun J, Vera JC, Drnevich J, Lin YT, Ke R, and Brooke CB. 2020. Single cell heterogeneity in influenza A virus gene expression shapes the innate antiviral response to infection. PLOS Pathogens. DOI: 10.1371/journal.ppat.1008671.
- Commentary in Nature Reviews Microbiology (https://www.nature.com/articles/s41579-020-0422-z)
Alnaji FG and Brooke CB. 2020. Influenza virus DI particles: defective interfering or delightfully interesting? PLOS Pathogens. DOI: 10.1371/journal.ppat.1008436.
Martin BE and Brooke CB. 2019. Flu shows the power of diversity. Cell. DOI: 10.1016/j.cell.2018.12.017.
Alnaji FG, Holmes JR, Rendon G, Vera JC, Fields CJ, Martin BE, and Brooke CB. 2019. Sequencing framework for the sensitive detection and precise mapping of defective interfering particle-associated deletions across influenza A and B viruses. J. Virol. DOI: 10.1128/JVI.00354-19.
Sun J and Brooke CB. 2018. Influenza A virus superinfection potential is regulated by viral genomic heterogeneity. mBio. DOI: 10.1128/mBio.01761-18.
Diefenbacher M, Sun J, and Brooke CB. 2018. The parts are greater than the whole: the role of semi-infectious particles in influenza A virus biology. Curr. Opin. in Virol. DOI: 0.1016/j.coviro.2018.07.002.
Kosik I, Ince WL, Gentles L, Oler AJ, Kosikova M, Angel M, Magadan J, Xie H, Brooke CB* and Yewdell JW*. 2018. Influenza A virus hemagglutinin glycosylation compensates for antibody escape fitness costs. PLOS Pathogens. DOI: 10.1371/journal.ppat.1006796. *Authors contributed equally
Brooke CB. 2017. Population diversity and collective interactions during influenza virus infection. J. Virol. PMID: 28855247.
Brooke CB*, Ince WL*, Bennink JR, and Yewdell JW. 2014. Influenza A virus nucleoprotein selectively decreases neuraminidase gene segment packaging while enhancing fitness and transmissibility. PNAS. 111(47): 16854-16859. *Authors contributed equally
Brooke CB, Ince WL, Wrammert J, Ahmed R, Wilson PC, Bennink JR, and Yewdell JW. 2012. Most influenza A virions fail to express at least one essential viral protein. J. Virol. 87(6): 3155-62.
- Selected as Issue Highlight
- F1000 Prime Recommendation (A. Garcia-Sastre and A. Baum. f1000.com/prime/717983224)
- Commentary by Carl Zimmer (Influenza: Our Incompetent Enemy. National Geographic
- Quoted in The Atlantic by Ed Yong (http://tinyurl.com/y66w7m8x)
Diefenbacher, M., Tan, T. J. C., Bauer, D. L. V., Stadtmueller, B. M., Wu, N. C., & Brooke, C. B. (2022). Interactions between Influenza A Virus Nucleoprotein and Gene Segment Untranslated Regions Facilitate Selective Modulation of Viral Gene Expression. Journal of virology, 96(10). https://doi.org/10.1128/jvi.00205-22
Ke, R., Martinez, P. P., Smith, R. L., Gibson, L. L., Mirza, A., Conte, M., Gallagher, N., Luo, C. H., Jarrett, J., Zhou, R., Conte, A., Liu, T., Farjo, M., Walden, K. K. O., Rendon, G., Fields, C. J., Wang, L., Fredrickson, R., Edmonson, D. C., ... Brooke, C. B. (2022). Daily longitudinal sampling of SARS-CoV-2 infection reveals substantial heterogeneity in infectiousness. Nature Microbiology, 7(5), 640-652. https://doi.org/10.1038/s41564-022-01105-z
Ke, R., Martinez, P. P., Smith, R. L., Gibson, L. L., Achenbach, C. J., McFall, S., Qi, C., Jacob, J., Dembele, E., Bundy, C., Simons, L. M., Ozer, E. A., Hultquist, J. F., Lorenzo-Redondo, R., Opdycke, A. K., Hawkins, C., Murphy, R. L., Mirza, A., Conte, M., ... Brooke, C. B. (2022). Longitudinal Analysis of SARS-CoV-2 Vaccine Breakthrough Infections Reveals Limited Infectious Virus Shedding and Restricted Tissue Distribution. Open Forum Infectious Diseases, 9(7), [ofac192]. https://doi.org/10.1093/ofid/ofac192
Ranoa, D. R. E., Holland, R. L., Alnaji, F. G., Green, K. J., Wang, L., Fredrickson, R. L., Wang, T., Wong, G. N., Uelmen, J., Maslov, S., Weiner, Z. J., Tkachenko, A. V., Zhang, H., Liu, Z., Ibrahim, A., Patel, S. J., Paul, J. M., Vance, N. P., Gulick, J. G., ... Burke, M. D. (2022). Mitigation of SARS-CoV-2 transmission at a large public university. Nature communications, 13(1), . https://doi.org/10.1038/s41467-022-30833-3
Alnaji, F. G., Reiser, W. K., Rivera-Cardona, J., te Velthuis, A. J. W., & Brooke, C. B. (2021). Influenza A Virus Defective Viral Genomes Are Inefficiently Packaged into Virions Relative to Wild-Type Genomic RNAs. mBio, 12(6), [e02959-21]. https://doi.org/10.1128/mBio.02959-21