We study reovirus-induced myocarditis (cardiac inflammation and tissue damage) in mice as a model for this important human disease. Recently, we have focused on the cardiac response to viral infection, with particular emphasis on viral induction of the antiviral cytokine interferon-beta in cardiac cells. We are interested in both the viral genes that stimulate this response, and the cardiac transcription factors and antiviral proteins that are central to protection against disease. Our approaches, using primarily molecular techniques, include the use of transgenic mice and primary cardiac myocyte cell cultures. This research is funded primarily by NIH.
Area(s) of Expertise
We study viral infections of the heart to identify the viral and host determinants of cardiac damage. Viral myocarditis is indicated as the second leading cause of sudden death in young adults. While viruses can induce immune-mediated pathology, it is likely that most viruses induce damage by directly injuring cardiac cells. Reovirus-induced myocarditis in neonatal mice reflects direct injury to the heart and offers an outstanding model for investigation. We use a wide range of approaches in vivo and in primary cardiac cell cultures to probe antiviral cell responses, particularly those that are unique to cardiac cells. We have found that the Type I interferon (IFN) response is an important determinant of protection against viral myocarditis. Our current investigations focus on: 1) the cardiac IFN response, 2) reovirus subversion of the IFN response, and 3) novel therapeutic approaches for viral myocarditis.
Research Specialist: Shannon Chiera
- Autocrine and paracrine interferon signalling as 'ring vaccination' and 'contact tracing' strategies to suppress virus infection in a host , PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES (2021)
- Interferon-lambda 3 Promotes Epithelial Defense and Barrier Function Against Cryptosporidium parvum Infection , CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY (2019)
- A Cytoplasmic RNA virus alters the function of the cell splicing protein SRSF2 , Journal of Virology (2017)
- NF-kappa B activation is cell type-specific in the heart , Virology (2017)
- Spontaneous activation of a MAVS-dependent antiviral signaling pathway determines high basal interferon-beta expression in cardiac myocytes , Journal of Molecular and Cellular Cardiology (2017)
- Use of RNA-seq to identify cardiac genes and gene pathways differentially expressed between dogs with and without dilated cardiomyopathy , American Journal of Veterinary Research (2016)
- Generating primary cultures of murine cardiac myocytes and cardiac fibroblasts to study viral myocarditis , Cardiomyocytes: methods and protocols (2015)
- An ITAM in a nonenveloped virus regulates activation of NF-kappa B, induction of beta interferon, and viral spread , Journal of Virology (2014)
- Replication of many human viruses is refractory to inhibition by endogenous cellular MicroRNAs , Journal of Virology (2014)
- A single-amino-acid polymorphism in reovirus protein mu 2 determines repression of interferon signaling and modulates myocarditis , Journal of Virology (2012)