Effects of influenza A virus infection on the pluripotency and proteome of induced pluripotent stem cells

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Zahedi Amiri, Ali
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Maternal influenza infection during pregnancy was reported multiple times as the possible cause of many defects and congenital anomalies. Apart from several cases of influenza-related miscarriage during various trimesters of pregnancy, some epidemiological data suggest a link between maternal influenza infection and genetic abnormalities in offspring. However, there are no reports yet describing cellular pathways that influence maternal influenza-induced congenital defects in the fetus. In the present study, using proteomic approaches, I utilized human induced pluripotent stem cells (hiPSCs) for modeling the intra-blastocyst infection with influenza virus to not only investigate the vulnerability and responses of pluripotent cells to this virus but also to determine the possible impacts of influenza on signaling pathways controlling embryogenesis. Immunoblotting and immunofluorescence microscopy indicated a considerable level of viral protein production in influenza A virus (IAV)-infected hiPSCs. However, IAV replication was restricted in these cells, but cell viability and pluripotency were negatively affected. These events occurred simultaneously with an excessive level of IAV-induced autophagy as well as cytopathic effects, suggesting the induction of spontaneous differentiation. Quantitative SOMAScan screening also indicated that minor changes in the proteome of hiPSCs corresponded to premature or abnormal spontaneous differentiation in these cells. Taken together, my results showed that IAV-modulated reduction in pluripotency of iPSCs is associated with significant activation of autophagy by this virus. Further investigations are required to explore the role of IAV-induced autophagy in leading pluripotent stem cells toward abnormal differentiation.
RNA virus, Influenza, Proteomics, SOMAScans, Pluripotency, Autophagy