| Name: |
| Tanya Miura |
| Title: |
| Assistant Professor |
| Degree: |
| Ph.D., 2000, Colorado State University |
| Phone: |
| (208) 885-4940 |
| Fax: |
| (208) 885-6518 |
| Email: |
| tmiura@uidaho.edu |
| Lab/Office Location: |
| LSS 149 |
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| Research Interests: |
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Regulation of the Immune Response to Coronavirus Infection in the Lung
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My lab studies viral pathogenesis and the host immune response to viral infection, specifically in the lung. We study rat
coronavirus infection of in vitro and in vivo models to understand how viral infection of the alveolar epithelium
initiates and orchestrates an immune response in the lung, and how this response contributes to viral clearance and/or
immunopathology. By understanding the balance between a beneficial (viral clearance) and a detrimental (immunopathology) immune
response in the lung, we can design better vaccination and treatment strategies for viral respiratory infections.
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For our in vitro studies, we isolate alveolar epithelial cells from rats and grow them in a way that maintains their
differentiated functions of a type I or type II alveolar epithelial cell. The type I cells make up the majority of the surface area
of the lung, and function in gas exchange and fluid homeostasis. The type II cells are the dividing cells of the alveolar
epithelium, and can migrate and trans-differentiate into a type I cell to repair damaged epithelium. Type II cells also secrete
surfactant lipids and proteins, which function in keeping the alveolus open and in innate defense of the lung. My lab studies virus
infection of these specialized cell types in vitro because they are important targets for viral infection in the lung and have a
significant influence on the downstream immune response. We study rat coronavirus (RCoV) as a model respiratory virus in its
natural host. Two strains of RCoV differ in tissue tropism and disease severity in the rat, yet they have both been isolated from
the lung during natural infection. I have shown that both of these strains, Parker’s RCoV (RCoV-P) and sialodacryoadenitis virus
(SDAV), infect primary rat type I and type II cell cultures. Furthermore, I have shown that RCoV infection of type I cells results
in expression of CXC chemokines, which is dependent partly on the proinflammatory cytokine IL-1. The primary function of CXC
chemokines is to recruit and activate neutrophils. Neutrophils are found in infected tissues early during coronavirus infection,
however their role in viral clearance and/or immunopathology during coronavirus infection is not known. My goals are to 1) Identify
pathways for neutrophil recruitment to the lung and activation upon RCoV infection; 2) Determine the viral and host cell components
that are required to initiate the IL-1 and CXC chemokine response from the alveolar epithelium; and 3) Examine the role of
neutrophils in the outcome of disease, with regard to viral clearance and immunopathology. These studies will define the early
events in the immune response upon viral infection of the lung and will lead to strategies for tipping the balance of the immune
response toward viral clearance and away from immune-mediated pathology.
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| Selected Publications: |
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T.A. Miura, J. Wang, R.J. Mason, and K.V. Holmes. 2006. Rat coronavirus infection of primary rat alveolar epithelial cells. Adv. Exp. Med. Biol., 581:31-356.
T.A. Miura, J. Wang, K.V. Holmes, and R.J. Mason. 2007. Rat coronaviruses infect rat alveolar type I epithelial cells and induce expression of CXC chemokines. Virology, 369:288-298.
T.A. Miura, E. Travanty, L. Oko, H. Bielefeldt-Ohmann, S.R. Weiss, N. Beauchemin, and K.V. Holmes. 2008. The spike glycoprotein of murine coronavirus MHV-JHM mediates receptor-independent infection and spread in the central nervous systems of Ceacam1a-/- Mice. J. Virol., 82:755-763.
E.C. Mossel, J. Wang, S. Jeffers, K.E. Edeen, S. Wang, G.P. Cosgrove, C.J. Funk, R. Manzer, T.A. Miura, L.D. Pearson, K.V. Holmes, and R.J. Mason. 2008. SARS-CoV replicates in primary human alveolar type II cell cultures but not in type I-like cells. Virology, 372:127-135.
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