Resistance to Infectious Disease

Our laboratory studies the immune response to infectious diseases, with a primary focus on the factors associated with initial innate recognition of the pathogen. The innate immune system is an evolutionarily conserved aspect of immunity. How the innate immune system recognizes and responds to infection can have profound affects on the adaptive response and ultimately the fate of the host. Understanding how stimulation of the innate immune system leads to different clinical outcomes is critical to understanding the genetic basis of disease resistance.  As part of this work, we use different in vitro and in vivo models to identify common responses across different host species.  Understanding how different species detect and respond to infection allows for the development of therapies which will work against large classes of pathogens and for a wide variety of animal species.  

Given the diversity of the host models used, a large aspect of our research involves identifying and characterizing the host response genes. 

Mechanism of Astrovirus Induced Disease
Astroviruses are small non-enveloped single stranded positive sense RNA viruses which are known to be a leading cause of acute diarrheal disease in the young of multiple mammalian and avian species.  Our laboratory uses an astrovirus associated with severe diarrheal disease of young turkeys, type-2 turkey astrovirus (TAstV-2), as a model for understanding the mechanism of disease and the host response involved in clearing the infection.  

Studies in our laboratory suggest astrovirus infection affects the apical expression and function of proteins involved in the absorption and transport of ions and nutrients.  These changes likely lead to an osmotic imbalance which is at least partially involved in the development of diarrhea.





Innate Resistance to Viral Infection
Normal host cells express several internal and external proteins responsible for detecting the presence of a virus, and initiating the response that will alert the immune system.  The proteins involved in this detection recognize pathogens based on pattern and are germline encoded.  Therefore allelic variation in these proteins can result in very different innate responses to virus infection and ultimately clinical disease.  Our laboratory has developed a panel of primary fibroblast cells from genetically distinct lines of chickens and have determined these cells respond differently to different types of viral challenges in vitro.  


Selected Publications
P. K. Nighot, A. Moeser, R. A. Ali, A. T. Blikslager, and M. D. Koci. Astrovirus infection induces sodium malabsorption and redistributes sodium hydrogen exchanged expression. Virology. 401:146-54, 2010.

E. Strain, L. A. Kelley, S. Schultz-Cherry, S. V. Muse, and M. D. Koci. Genomic Analysis of Closely Related Astroviruses. Journal of Virology. 82: 5099-5103, 2008. 

M. D. Koci, L. A. Kelley, D. L. Larsen, and S. Schultz-Cherry. Astrovirus-induced synthesis of nitric oxide contributes to virus control during infection. Journal of Virology. 78:1564-1574, 2004.

M. D. Koci, L. A. Moser, L. A. Kelley, D. L. Larsen, C. C. Brown, and S. Schultz-Cherry. Astrovirus induces diarrhea in the absence of inflammation and cell death. Journal of Virology. 77:11798-11808, 2003.
PERSONNEL
(Assistant Professor, Viral Immunology)
Jim Croom
(Professor, Nutrtional Physiology)
Rizwana Ali
(Research Specialist)
Tamer Helmy
(Post-Doc)
Anne Ballou
(PhD Student)


CONTACT INFO
919.515.5388 (office)
919.515.5393 (lab)
919.515.2625 (fax)
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