Respiratory failure resulting from chronic infection and inflammation of the airways still represent the primary cause of death for most individuals with cystic fibrosis (CF). Chronic bacterial infections are the main cause of lung damage with less known about the role of viral infections. As such, a better understanding of infection related pathology of the CF airways is needed. Bacteria remain the primary pathogens associated with airway inflammation, although additional important opportunistic pathogens are emerging. Besides a constitutive inflammatory state, CF typically has a course of exacerbations and remissions of pulmonary complaints, suggesting that external factors influence this course. In this regard, viral infections are often associated with worse respiratory symptoms in CF disease. Although it has been demonstrated that several members of the Polyomavirus (PyV) family infect the human respiratory tract and appear to be significant human pathogens in immunosuppressed people, remains unclear if these viruses may be important trigger of exacerbation in CF. Specifically, to date, the role played by Merkel cell Polyomavirus (MCPyV), in patients with a high risk of pulmonary morbidity such as CF patients, is poorly studied. In this regard, to improve our knowledge on the possible pathogenic involvement of MCPyV in CF, it will be proposed to study, in vivo, the MCPyV prevalence in CF patients and to analyze the simultaneous presence of MCPyV with respect to the bacterial colonization status in order to understand the impact of viral-bacterial co-infections in the CF airways. Moreover, since a much less information regarding the natural biology of MCPyV is, to date, available, it will be proposed to setting up an in vitro model primary bronchial/tracheal epithelial cells-based to understand if this cell types support MCPyV¿s growth, to study the MCPyV¿s life cycle and MCPyV¿s role in tumorigenesis.
Progressive pulmonary disease is the primary cause of morbidity and mortality in CF patients. In recurrent pulmonary exacerbation, the role of chronic bacterial infections is well-known whereas, the role of viral infections is still debated. The pathogenic role of Polyomaviruses (PyVs), such as BKPyV and JCPyV, is well described in immunosuppressed people, as well as it has been demonstrated the presence of WUPyV and KIPyV in respiratory samples of haematology/oncology and AIDS patients. Since only one study evaluated the prevalence of MCPyV in patients suffering from CF and although has not been established if this virus may be important triggers of exacerbation in CF, our proposal could gain new insights into a potential pathogenic role played by MCPyV in CF. In this framework, we will investigate the presence of MCPyV DNA in the upper and lower respiratory tract of CF patients and analyze the simultaneous presence of MCPyV with respect to the bacterial colonization status in order to understand the impact of viral-bacterial co-infections in the CF airways. Last, a further strength of the project regarding the in vivo study, will be also represented by the use of the same routinely collected respiratory samples to perform the virological analysis, allowing the collection of a very large numbers of samples from CF patients in a relative short period.
Mechanistic studies to fully investigate MCPyV molecular biology and oncogenic mechanisms have been hampered by a lack of adequate cell culture models. The first and the only one cell culture infection model for MCPyV available was described by Liu and co-workers. They discovered that primary human dermal fibroblasts support robust MCPyV infection both in vitro and ex vivo. Starting from this, building other models that support MCPyV infection could facilitate the establishment of systems to fully elucidate the MCPyV infectious life cycle and MCPyV-induced tumorigenesis in vivo. Our effort to setting up an in vitro model primary bronchial/tracheal epithelial cells-based, can enrich the field of knowledge of MCPyV¿s biology.