Christopher Byron Brooke

cbrooke@illinois.edu

390A Burrill Hall
601 South Goodwin Avenue
Urbana, IL 61801
Office: (217) 265-0991
Lab: (217) 244-4917

Mail to: B103 CLSL, MC-110
601 South Goodwin Avenue
Urbana, IL 61801
Lab Page

Christopher Byron Brooke

Assistant Professor

Research Topics

Host-Pathogen Interactions, Molecular Evolution, Molecular Immunology, Regulation of Gene Expression, Virology

Education

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

Mechanisms of influenza virus adaptation

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 facilitate influenza virus host adaptation, transmissibility, and immune escape. Defining these mechanisms is critical for understanding influenza pathogenesis, as well as for improving vaccines, therapeutics, and pandemic surveillance.

My laboratory is primarily focused on understanding how the genetic architecture of influenza virus promotes and influences viral adaptation and immune evasion. The influenza virus genome consists of eight distinct RNA gene segments, all of which are required to encode a productive infection. Many of our studies build on our observation that the vast majority of influenza virus particles carry a functionally incomplete set of gene segments, rendering them invisible to traditional infectivity assays. Rather than serving as dead-end products, widespread co-infection in vivo allows these incomplete, or semi-infectious, particles to replicate and exchange gene segments through complementation. The virus can alter the gene segment content of the semi-infectious particle population in surprising ways as it adapts to changing host conditions. These adaptive alterations provide a great opportunity to dissect the critical role that semi-infectious particles play in influenza virus replication and evolution.

We are also interested in using population genetics approaches to better understand influenza virus immune escape, pathogenicity, and transmission. We are developing improved methods for ultra-deep viral population sequencing that allow us to track minor sequence variants and measure positive selection across the influenza virus genome with unprecedented sensitivity and accuracy.

Areas of study within the lab include:

Determining the role of semi-infectious particles and viral cooperativity during replication, transmission, and evolution.

Defining the epistatic interactions between viral gene segments and determining how they promote and/or constrain viral evolution.

Using single-particle/single-cell analysis of influenza virus infection to examine the interplay between individual viral gene products and the host.

Employing ultra-deep population sequencing methods to understand how influenza populations maintain fitness while evading host immunity.

Representative Publications

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. 2014. Biological activities of ‘noninfectious’ influenza A particles. Future Virol. 9(1):41-51.
• Selected as Issue Highlight

Das SR, Hensley SE, Ince WL, Brooke CB, Subba A, Delboy MG, Russ G, Gibbs JS, Bennink JR, and Yewdell JW. 2013. Defining Influenza A Virus Hemagglutinin Antigenic Drift by Sequential Monoclonal Antibody Selection. Cell Host Microbe. 13(3): 314-323.
• Cover Article

Brooke CB and Yewdell JW. 2013. Host versus flu: antibodies win a round? Nat. Struct. Mol. Biol. 20(3):245-6.

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

Yewdell JW and Brooke CB. 2012. Monocytes, viruses, and metaphors: Hanging the Trojan horse. Cell Cycle. 11(9): 1748-9

Hou W, Gibbs JS, Lu X, Brooke CB, Roy D, Modlin RL, Bennink JR, and Yewdell JW. 2012. Viral infection triggers rapid differentiation of human blood monocytes into dendritic cells. Blood. 119(13):3128-31.

Brooke CB, Schaefer A, Matsushima GK, White LJ, and Johnston RE. 2012. Early activation of the host complement system is required to restrict CNS invasion and limit neuropathology during Venezuelan equine encephalitis virus infection. J. Gen. Virol. 93(4):797-806.

Schaefer A, Brooke CB, Whitmore AC, and Johnston RE. 2011. The role of the blood brain barrier during Venezuelan equine encephalitis virus infection. J. Virol. 85(20):10682-90.

Brooke CB, Deming DJ, Whitmore AC, White LJ, and Johnston RE. 2010. T cells facilitate recovery from Venezuelan equine encephalomyelitis virus-induced encephalomyelitis in the absence of antibody. J. Virol. 84(9):4556-68.