Respiratory viral infections, particularly by human rhinoviruses (HRV), play important roles in inception, development, exacerbation and chronicity of asthma. This program is focused on defining interactions between factors regulating HRV replication and host immune response to viral infection that affect the severity of associated respiratory illness. Each of the projects will use viral diagnostics, and Projects II and 111 require specialized preparations of purified viruses and molecular reagents related to viral biology. The Virology Core is established to provide viral diagnostics and HRV molecular reagents to each of the three proposed projects. Project I will be supported with a repertoire of sensitive and accurate molecular detection assays to identify all common respiratory viruses and the individual species/type/strain of HRV. The viral loads will be quantified by qPCR in a subset of HRV-positive nasal samples from human subjects of Project I for subsequent virus isolation, complete genome sequencing, cDNA cloning and use in Projects ll-lll. In addition, this core will support the in vitro experiments of Projects l-lll by supplying (1) high-titer and uniform HRV virus stocks, including purified viruses (native, radiolabeled and inactivated) of selected HRV serotypes and strains, infected cell lysates of 100 classical HRV-A and HRV-B serotypes and newly identified HRV-C strains, (2) various anti-HRV antibodies, (3) cDNA clones (infectious, chimeric, reporter, replicons) of selected HRV-A, HRV-B and HRV-C types/strains, (4) performing infectivity assays (plaque and TCID50), and (5) culture of airway epithelial cells

Public Health Relevance

Viral respiratory infections with associated airway obstruction and wheezing are the most frequent cause of hospitalization in infants, and in children and adults with asthma. Defining interactions between factors regulating HRV replication and host immune response to viral infection that affect the severity of associated respiratory illness could lead to new strategies to reduce virus-induced wheezing illnesses, and decrease acute exacerbations in people with asthma.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI104317-02
Application #
8790529
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
DUNS #
City
Madison
State
WI
Country
United States
Zip Code
53715
Yang, Zhonghui; Bochkov, Yury A; Voelker, Dennis R et al. (2018) Identification of a Novel Inhibitor of HRV Replication and Inflammation in Airway Epithelial Cells. Am J Respir Cell Mol Biol :
Hasegawa, Kohei; Jartti, Tuomas; Bochkov, Yury A et al. (2018) Rhinovirus Species in Children with Severe Bronchiolitis: Multicenter Cohort Studies in the US and Finland. Pediatr Infect Dis J :
Yin, John; Redovich, Jacob (2018) Kinetic Modeling of Virus Growth in Cells. Microbiol Mol Biol Rev 82:
Scully, Erik J; Basnet, Sarmi; Wrangham, Richard W et al. (2018) Lethal Respiratory Disease Associated with Human Rhinovirus C in Wild Chimpanzees, Uganda, 2013. Emerg Infect Dis 24:267-274
Ludka-Gaulke, Tiffany; Ghera, Princy; Waring, Stephen C et al. (2018) Farm exposure in early childhood is associated with a lower risk of severe respiratory illnesses. J Allergy Clin Immunol 141:454-456.e4
Teo, Shu Mei; Tang, Howard H F; Mok, Danny et al. (2018) Airway Microbiota Dynamics Uncover a Critical Window for Interplay of Pathogenic Bacteria and Allergy in Childhood Respiratory Disease. Cell Host Microbe 24:341-352.e5
Bashir, Hiba; Grindle, Kristine; Vrtis, Rose et al. (2018) Association of rhinovirus species with common cold and asthma symptoms and bacterial pathogens. J Allergy Clin Immunol 141:822-824.e9
Kim, Chang Keun; Callaway, Zak; Gern, James E (2018) Viral Infections and Associated Factors That Promote Acute Exacerbations of Asthma. Allergy Asthma Immunol Res 10:12-17
Gern, James E; Lee, Wai Ming; Swenson, Cheri A et al. (2018) Development of a Rhinovirus Inoculum using a Reverse Genetics Approach. J Infect Dis :
Leino, Annamari; Lukkarinen, Minna; Turunen, Riitta et al. (2018) Pulmonary function and bronchial reactivity 4 years after the first virus-induced wheezing. Allergy :

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