Recent studies utilizing PCR-based diagnostics have demonstrated that rhinovirus (HRV) is an important cause of lower respiratory illness including bronchiolitis, influenza-like illness, and exacerbations of chronic lung diseases such as asthma, cystic fibrosis, and chronic obstructive lung disease (COPD). In addition, HRV wheezing illnesses in the first three years of life are among the strongest risk factors for subsequent asthma. The lack of specific treatments and preventive strategies for more severe HRV illnesses and exacerbations of asthma is a major unmet medical need. To address this therapeutic gap, we propose a novel program of three interrelated projects to identify risk factors and pathogenic mechanisms related to the virus, host immune response, and environment that determine the severity of HRV illnesses. The clinical centerpiece of the program is the proposed Wisconsin Infant Immune &Illness Surveillance Cohort (""""""""WISC"""""""", Project 1), which will define how a naturally-occurring intervention, farm exposure in early childhood, enhances immune maturation and antiviral responses, and reduces morbidity from viral respiratory illnesses. Defining distinct farm-related patterns of immune maturation that mediate protection from viral illnesses will provide a road map for new preventive approaches intended to minimize respiratory morbidity for children growing up in other environments. In Project 2, Dr. Ann Palmenberg and colleagues propose to use novel tissue culture systems and molecular approaches to define the pathogenesis of the newly described HRV-C species, focusing on identification of the cellular receptor and clinical consequences of unique 2Apro structure and biochemistry. Finally, in Project 3, Dr. John Yin will use novel techniques (fluorescent-tagged HRVs and indicator cell lines, real-time fluorescent microscopy) to reveal how HRV replication in single cells stimulates immune responses and define mechanisms of spread to neighboring cells. Collectively, these three projects will extensively share clinical samples, expertise and conceptual advances to identify new targets for the treatment and prevention of HRV infections.
Rhinoviruses, originally known as common cold viruses, also cause lower respiratory illnesses such as childhood wheezing, influenza-like illness, and exacerbations of asthma and COPD. Unfortunately, no treatments or vaccines are available for HRV infections. We propose to identify new environmental and molecular determinants of HRV illness severity that will serve as a basis for new treatment strategies.
|Griggs, Theodor F; Bochkov, Yury A; Basnet, Sarmila et al. (2017) Rhinovirus C targets ciliated airway epithelial cells. Respir Res 18:84|
|Barkal, Layla J; Procknow, Clare L; Álvarez-García, Yasmín R et al. (2017) Microbial volatile communication in human organotypic lung models. Nat Commun 8:1770|
|Bjerregaard, Asger; Laing, Ingrid A; Poulsen, Nadia et al. (2017) Characteristics associated with clinical severity and inflammatory phenotype of naturally occurring virus-induced exacerbations of asthma in adults. Respir Med 123:34-41|
|Kloepfer, Kirsten M; Sarsani, Vishal K; Poroyko, Valeriy et al. (2017) Community-acquired rhinovirus infection is associated with changes in the airway microbiome. J Allergy Clin Immunol 140:312-315.e8|
|Palmenberg, Ann C (2017) Rhinovirus C, Asthma, and Cell Surface Expression of Virus Receptor CDHR3. J Virol 91:|
|Timm, Andrea C; Warrick, Jay W; Yin, John (2017) Quantitative profiling of innate immune activation by viral infection in single cells. Integr Biol (Camb) 9:782-791|
|Bashir, Hiba; Grindle, Kristine; Vrtis, Rose et al. (2017) Association of rhinovirus species with common cold and asthma symptoms and bacterial pathogens. J Allergy Clin Immunol :|
|Turunen, Riitta; Vuorinen, Tytti; Bochkov, Yury et al. (2017) Clinical and Virus Surveillance After the First Wheezing Episode: Special Reference to Rhinovirus A and C Species. Pediatr Infect Dis J 36:539-544|
|Anderson, Halie M; Lemanske Jr, Robert F; Evans, Michael D et al. (2017) Assessment of wheezing frequency and viral etiology on childhood and adolescent asthma risk. J Allergy Clin Immunol 139:692-694|
|Bochkov, Yury A; Gern, James E (2016) Rhinoviruses and Their Receptors: Implications for Allergic Disease. Curr Allergy Asthma Rep 16:30|
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