Abstract P431: Trypanosoma Cruzi Induces Alterations In The Piwi-interacting Rna Expression Profile Of Human Cardiomyocytes During The Early Phase Of Infection

Abstract

Listen

Translate article

Trypanosoma cruzi , the causative agent of Chagas Heart Disease, is an intracellular parasite that was originally endemic to Central and South America. However, due to globalization, the disease is now present in most industrialized countries. About 40% of T. cruzi infected individuals will develop a form of cardiomyopathy including aneurysms, arrythmias, fibrosis, hypertrophy. Host gene expression profile has been shown to be significantly dysregulated to facilitate parasite infection and pathogenesis. The role of gene expression regulatory molecules such as small noncoding RNAs during infection has yet to be fully elucidated. In this study, we aim to evaluate if the parasite can regulate the expression profile of an emerging class of small non-coding RNAs, piwi-interacting RNAs (piRNAs), during the early phase of T. cruzi infection in primary human cardiacmyocytes (PHCM). We challenged PHCM with invasive T. cruzi trypomastigotes and purified RNA for RNA sequencing and analysis. We found that an average of 21,595,866 clean reads (88.4%) mapped to the human reference genome. We observed that the parasite induced significant differential expression of 217 host piRNAs using NOISeq. Furthermore, we employed miRanda and RNA22 to predict mRNA targets of the differentially expressed piRNA. We utilized WEBGESTALT to map piRNAs of interest to their biological pathways. In silico analysis showed that both dysregulated known and novel piRNAs could target several genes of interest including NFATC2, which has been reported to play an important role in the onset of cardiomyopathies reported in Chagasic patients. Our novel findings are the first to show that T. cruzi can induces differential expression of piRNAs during the early phase PHCM infection.