Comparative study of Human Respiratory Syncytial Virus (HRSV) infection in cells of lymphoid and epithelial origin: expression of microRNAs, kinases, and inflammasome activation

Abstract

In summary, as part of their evolution, both viruses and host cells are capable to manipulate the miRNAome, kinases, and inflammasome activation to regulate the overall immune response in a virus and cell type specific fashion. Understanding changes in miRNA and kinase-expression profiles, identifying target genes and their contribution to the pathogenesis of inflammation and/or HRSV persistence, may help with the intricate mechanisms of HRSV-host interaction. In addition, results obtained until now are only related to epithelial cells, whereas mechanisms involved in HRSV infection of lymphoid human cells are virtually unknown. A safe vaccine has not been developed yet because there is a lack of knowledge on how HRSV interacts with host cell and modulates immune response.The major goal of this project is to understand the mechanism by which HRSV interacts with host cell, focusing mainly in the comparison between epithelial and lymphoid cells, detecting patterns of modulated cell factors such as miRNAs, kinases, and inflammasome activation during HRSV infection. Therefore, BEPE project will help to understand the important results already obtained in my currently ongoing postdoctoral project (FAPESP- Process 2012/19131-5). It will be developed in collaboration with the laboratory of Dr. Ralph Tripp, who is a widely known reference in studies of HRSV/host cell interaction, with several recognized publications in this field. Furthermore, this BEPE project will improve the knowledge of mechanisms involved in HRSV pathogenesis, taking advantage of a collaboration with Dr. Eurico Arruda's laboratory at USP in Brazil, where the previous results have been obtained, and where the human tonsil tissue samples were collected an are in storage. Such collaboration may be fruitful for bringing expertise back to Brazil, thus helping the understanding the spatial and temporal host genes affected by HRSV in cells from different origins. This may in turn helping with the development of future HRSV disease intervention strategies.