PIWIL4 and piRNAs in RSV Infection

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PROJECT SUMMARY/ABSTRACT Acute respiratory tract infections are a leading cause of morbidity and mortality in children worldwide. Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in children, elderly and immunocompromised patients, as well as of asthma exacerbations. No effective treatment or vaccine for RSV is currently available, and many fundamental questions regarding the pathogenesis of RSV-induced lung disease have yet to be answered. Small non-coding RNAs (sncRNAs) have been found to regulate many cellular processes, including host-virus interactions. RSV infection can significantly alter the expression profile of host sncRNAs, and several types of sncRNAs, such as miRNA and tRFs, have been shown to play a significant role in RSV replication and virus-induced host responses. In recent studies, we found that RSV infection alters the expression of piwi RNAs, (piRNAs), one of the largest classes of sncRNA molecules expressed in animal cells. Although the role of piRNAs was initially confined to gonad development, recent studies have identified specific expression profile of piRNAs from multiple organs and cell types, and different profiles have been associated with several diseases, including various types of cancers, cardiovascular diseases, autoimmune and neurodegenerative disorders. Surprisingly, almost nothing is known regarding piRNA generation/function and PIWI proteins in the context of viral infections. Identification of patterns and details of human sncRNAs generation has significantly helped understanding how they modulate host responses in the context of viral infections. The outcome of the proposed studies will lead to new knowledge regarding the role of piRNAs in RSV-induced cellular responses, potentially identifying novel therapeutic targets and/or bio-markers for disease diagnosis and prognosis.