Research Interest: Pathogenesis of mammalian reovirus
Ph.D.: University of Wisconsin-Madison, Madison, WI
Postdoctoral Fellowship: Vanderbilt University, Nashville, TN
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My laboratory seeks to uncover mechanisms of viral pathogenesis. We use mammalian orthoreovirus (reovirus) as an experimental system to define viral and host determinants that govern viral diseases. Reoviruses are non-enveloped viruses with genomes consisting of 10 segments of dsRNA (right). Our research is built on three focus areas. First, we are interested in determining how reovirus spreads within the host via the bloodstream. Reoviruses infect their hosts via gastrointestinal or pulmonary routes and traffic to the bloodstream which allows the virus to access every organ system in the body, including the central nervous system. We seek to understand how reoviruses access the bloodstream and move throughout the host to target organs where it causes disease. Second, we are working to define how reovirus activates and resists type-I interferon responses. Type-I interferons are a component of the innate immune system that are critical for control and clearance of all viral infections. We use reoviruses as a model to uncover how viruses activate type-I interferon responses, as well as how they overcome these responses to replicate efficiently. Finally, we have a focus on understanding how reoviruses produce their proteins in infected cells. Cell employ a variety strategies to prevent viruses from co-opting the host translational machinery to preferentially synthesize viral proteins instead of cellular proteins. Our work tries to determine how reoviruses overcome these defenses to generate the viral proteins needed for productive viral replication, which ultimately leads to viral disease.
We have identified a key role for one of the reovirus nonstructural proteins, sigma 1s, in each of these three focus areas (by non-structural protein, we mean a protein that it is not part of the virus particle, not that it doesn’t have a structure). Ongoing work in the lab combines genetic, biochemical, and cell biological approaches to delineate how sigma 1s promotes viral protein synthesis and facilitates resistance to type-I interferon. We employ a small animal model that allows us to determine how our findings in cultured cells impact reovirus pathogenesis.
Current Lab Members
- LeKevia Cobb, Graduate Student
- Marcelle DinaZita, Graduate Student
- Michael Eledge, Graduate Student
- Movya Kouassi, Research Technician
- Ryan Mann, Research Technician
- Ani Paredes (Research Technician)
- Emily Simon, M.D. (Research Technician) – Family Medicine Resident, UAMS Northeast Medical Center
- Joseph Koon (Research Technician) – UAMS College of Medicine
- Matthew Phillips, Ph.D. (Graduate Student) – Postdoctoral Fellow, University of Florida (Karst Lab)
- Johnasha Stuart, Ph.D. (Graduate Student) – Postdoctoral Fellow, Emory University (Grakoui Lab)
- Morgan Howells (Research Technician) – UAMS College of Medicine
- Stuart JD, Holm GH, and Boehme KW. Differential delivery of genomic dsRNA causes reovirus strain-specific differences in IRF3 activation. J Virol. Apr 13;92(9). pii: e01947-17. doi: 10.1128/JVI.01947-17. 2018.
- Phillips MB, Stuart JD, Simon EJ, Boehme KW. Non-structural protein σ1s is required for optimal reovirus protein expression. J Virol. 92:e02259-17. https://doi .org/10.1128/JVI.02259-17. 2018.
- Simon EJ, Howells MA, Stuart JD, Boehme KW. Serotype-Specific Killing of Large Cell Carcinoma Cells by Reovirus. Viruses 9(6) 140, 2017.
- Stuart JD, Phillips MB, Boehme KW. Reverse Genetics for Mammalian Orthoreovirus. Methods Mol Biol. 1602: 1-10, 2017.
- Bouziat R, Hinterleitner R, Brown JJ, Stencel-Baerenwald JE, Ikizler M, Mayassi T, Meisel M, Kim SM, Discepolo V, Pruijssers AJ, Ernest JD, Iskarpatyoti JA, Costes LM, Lawrence I, Palanski BA, Varma M, Zurenski MA, Khomandiak S, McAllister N, Aravamudhan P, Boehme KW, Hu F, Samsom JN, Reinecker HC, Kupfer SS, Guandalini S, Semrad CE, Abadie V, Khosla C, Barreiro LB, Xavier RJ, Ng A, Dermody TS, Jabri B. Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science 356(6333): 44-50, 2017.
- Boehme KW, Ikizler M, Iskarpatyoti JA, Wetzel JD, Willis J, Crowe JE Jr, LaBranche CC, Montefiori DC, Wilson GJ, Dermody TS. Engineering Recombinant Reoviruses To Display gp41 Membrane-Proximal External-Region Epitopes from HIV-1. mSphere 1(3): pii: e00086-16, 2016.
- Boehme KW, Hammer K, Tollefson WC, Konopka-Anstadt JL, Kobayashi T, Dermody TS. Nonstructural protein σ1s mediates reovirus-induced cell cycle arrest and apoptosis. J Virol. 87(23):12967-79, 2013.
- Boehme, K.W., Frierson, J.M., Konopka, J.L., Kobayashi, T., and Dermody, T.S. The reovirus σ1s protein is a determinant of hematogenous but not neural viral dissemination in mice. J. Virol. 85: 11781-90, 2011.
- Boehme, K.W., Guglielmi, K.M., and Dermody, T.S. Reovirus nonstructural protein σ1s is required for establishment of viremia and systemic dissemination. Proceedings of the National Academy of Sciences, USA. 106: 19986-19991, 2009.