Pathogenesis of noroviruses, innate immune responses to norovirus infection, and molecular mechanisms of norovirus replication.
Human noroviruses cause a majority of gastroenteritis outbreaks across the globe and are the leading cause of severe childhood diarrhea and foodborne disease outbreaks in the United States. They are likely an even more significant problem in impoverished parts of the world, as supported by a survey that estimates they cause over one million clinic visits and 200,000 deaths in young children annually. Development of effective and long-lasting norovirus vaccines as well as antiviral therapies are thus of critical need. Unfortunately, the human norovirus field has long been crippled by the lack of an in vitro cell culture system.
My laboratory has recently revealed that B cells are targeted by both murine and human noroviruses, and have found that human noroviruses replicate in B cells in vitro. During these studies, we also made the fascinating discovery that norovirus infection is enhanced by commensal bacteria both in cells and in vivo during natural infections. As we now work to optimize this in vitro infection system, we hope that it will represent a major breakthrough for the norovirus field.
One of our immediate goals is to elucidate host and viral factors that regulate human norovirus infection. This information will provide key insight into critical host-virus interactions that can be targeted in future therapeutic and prevention strategies. Identifying host restriction factors may also facilitate the development of a more robust cell culture system. Our other immediate goal is to determine the impact of bacterial engagement on norovirus infection, both mechanistically at the cellular level and immunologically at the organismal level. Our overall research program aims to contribute to norovirus vaccine and antiviral drug development in the long-term.
Lab Personnel
Stephanie Karst
Marco Grodzki
Matthew B Phillips
Current Research Projects/Grants
NIH/NIAID
1R01AI141478
11/25/2018-10/31/2023
Title: Suppression of Enteric Norovirus Infection by Microbiota-Regulated Bile Acids
Role: PI
Budget: $1,817,466 direct costs (5 yrs)
NIH/NIAID
1R01AI123144
12/01/2016–11/30/2021
Title: Identification of Host and Viral Determinants of Human Norovirus B cell Infection
Role: PI; 25% effort
Budget: $1,649,338 direct costs (5 yrs)
UF Opportunity Fund 12482
06/01/2017-05/31/2019
Title: The Role of Human CD300 Molecules in Human Norovirus Infection of B cells
Role: PI (co-PI Mavis Agbandje-McKenna; Department of Biochemistry)
Budget: $95,000 direct costs (2 yrs)
NIH/NIAID
1R01AI116892-01
02/16/2015-01/31/2020
Title: Role of Intestinal Bacteria in Human Norovirus Infection
Role: PI; 20% effort
Budget: $1,250,000 direct costs (5 yrs)
Completed Research Support
Takeda Pharmaceuticals
04/01/2016-03/31/2018
Title: Refinement of the Human Norovirus Cultivation System
Role: P.I.
Direct costs: $275,000 (2 yrs)
NIH/NIAID
1R56 AI123144
03/01/16–11/30/16
Title: Identification of Host and Viral Determinants of Human Norovirus B cell Infection
Role: PI
Budget: $338,034 direct costs (1 yr)
UF Opportunity Fund 00093472
05/21/2014-05/20/2016
Title: Intestinal Epithelial Cell Contributions to Permissiveness of Norovirus Infection of B Cells
Role: co-PI (PI Shannon Wallet; College of Dentistry)
Direct costs (2 yr): $84,500
Center for Produce Safety at the University of California, Davis
01/01/2014-12/31/2015
Title: Effect of physicochemical and biological parameters on survival, persistence, and transmission of norovirus in water and on produce
Role: co-PI
Direct costs (2 yr): $324,403
UF Emerging Pathogens Institute
01/15/2013-06/14/2015
Title: Elucidating the contribution of nutrition-regulated mucosal immune responses to the control of norovirus infections
Role: Sponsor
Direct costs: $85,912
R01AI081921-01
NIH/NIAID
09/07/2009-06/30/2014
Title: Lack of protective immunity to murine norovirus infection
Role: P.I.; 6 calendar months
Direct costs (5 yrs): $936,878
Global Emerging Infections Surveillance (GEIS) C0654_12_UN (P.I. Afsar Ali)
Department of Defense, Armed Forces Health Surveillance Center
02/15/12-09/30/12
Title: Clinical surveillance for enteric pathogens in Haiti
Role: Co-P.I., 1.2 calendar months
Directs costs: $13,480 (of $220,000 total budget)
1R21AI082310-01
NIH/NIAID
05/15/10-04/30/12
Title: Persistent norovirus infection impairs protective immunity
Role: P.I.
Direct costs (2 yrs): $273,750
LA Board of Regents Research Competitiveness Subprogram Grant
07/01/08-12/31/10
Title: The contribution of mucosal interferon to the control of enteric norovirus infection
Role: P.I.
Direct costs (3 yrs): $101,874
NIH, COBRE P20-RR018724-03 (O’Callaghan Grant P.I.)
05/01/08-04/30/10
Center for Biomedical Research Excellence: Center for Molecular and Tumor Virology
Title: Persistent norovirus infection of lymphoid tissue impairs protective immunity
Role: Project P.I.
Direct costs (2 yrs): $300,000 (Karst, Project 1)
LSUHSC-S Intramural Research Award in Gene Therapy
01/01/09-12/31/09
LA Gene Therapy Consortium
Title: Attenuated norovirus vectors for oral tolerance-based therapy
Role: P.I.
Direct costs (1 yr): $25,000
LSUHSC-S Intramural Research Support Award
01/01/08-12/31/08
Title: The molecular mechanism of interferon-mediated inhibition of murine norovirus replication
Role: P.I.
Direct costs: $25,000
NIH, COBRE P20-RR018724-01 (O’Callaghan Grant P.I.)
08/01/05-04/30/08
Center for Biomedical Research Excellence: Center for Molecular and Tumor Virology
Title: Replication of murine noroviruses
Role: Project P.I.
Direct costs: $546,344 (Karst, Project 4)
NIH, MRCE Clinical/Translational Fellowship
07/01/04-06/30/05
Title: A lariat form of a norovirus genome
Stipend award (2 yrs): $36,000/yr
Recent Publications
Huys, K.R. Grau, and S.M. Karst. Rotavirus and Norovirus Vaccines. In Hirisho Kiyono and David Pascual (Eds), Mucosal Vaccines 2nd Edition: Innovation for Preventing Infectious Diseases. Elsevier Academic Press (to be published in 2019).
K. Jones and S.M. Karst. Enteric Viruses Hitch a Ride on the Evolutionary Highway. Invited Preview. Cell Host & Microbe 23(1):5-5 (2018).
R. Grau, A.N. Roth, S. Zhu, A. Hernandez, N. Colliou, B.B. DiVita, D.T. Philip, C.J. Riffe, B.I. Giasson, S.M. Wallet, M. Mohamadzadeh, and S.M. Karst. The Major Targets of a Norovirus during Acute Infection are Immune Cells in the Gut-Associated Lymphoid Tissue. Nature Microbiology 2(12):1586-1591 (2017).
Yaren, K.M. Bradley, P. Moussatche, S. Hoshika, Z. Yang, S. Zhu, S.M. Karst, and S.A. Benner. A Norovirus Detection Architecture Based on Isothermal Amplification and Expanded Genetic Systems. J Virol Methods 237:64-71 (2016).
M. Karst. Viral Safeguard: The Enteric Virome Protects against Gut Inflammation. Invited Preview. Immunity 44(4):715-718 (2016).
M. Karst and S.A. Tibbetts. Recent Advances in Norovirus Biology. Invited Review. Journal of Medical Virology 88(11):1837-43 (2016).
Zhu, M.K. Jones, D. Hickman, S. Han, W. Reeves, and S.M. Karst. Norovirus Antagonism of B cell Antigen Presentation Results in Impaired Control of Acute Infection. Mucosal Immunology 9(6):1559-1570 (2016).
M. Karst. The Influence of Commensal Bacteria on Infection with Enteric Viruses. Invited Review. Nature Reviews Microbiology 14:197-204 (2016).
R. Garg and S.M. Karst. Interactions between Enteric Viruses and the Gut Microbiota (Chapter 5.2). In Lennart Svensson, Ulrich Desselberger, Harry B. Greenberg, and Mary K. Estes (Eds), Viral Gastroenteritis 1st Edition: Molecular Epidemiology and Pathogenesis. Elsevier Academic Press (2016; print ISBN: 9780128022412, eBook ISBN: 9780128026595) p. 535-543.