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Antiviral mechanisms based on RNA interference
My research interests focus on the study of a new layer of mammalian innate immunity based on RNA interference (RNAi). This mechanism is a well-established antiviral defence in plants and invertebrates in which long double-stranded RNA (dsRNA) derived from viral replication is cleaved by the enzyme Dicer into small interfering RNA (siRNA). These small RNAs are loaded into an effector complex and guide the cleavage of target RNAs such as the viral genome and viral transcripts. During my postdoctoral studies, I opted to explore the potential existence of antiviral RNAi in mammalian cells. I uncovered that this mechanism of antiviral defence is intact and effective in mouse embryonic stem cells but is highly reduced in differentiated cells. In these latter cells, the introduction of long dsRNA triggers RNAi but it is masked or inhibited by the interferon pathway. My research now aims at understanding the cell types and contexts in which this ancestral mechanism plays a role in antiviral defence.
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