How the immune system distinguishes self from viral infection

A major early-career grant is set to advance research into one of immunology’s most fundamental questions: How the body tells friend from foe at the molecular level.

Dr Alex Price at the Wistar Institute has been awarded a five-year, $2.53 million grant from the National Institute of General Medical Sciences to investigate how immune cells recognise and respond to viral infection without turning against healthy tissue.

“Our cells rapidly detect infection by distinguishing viral RNA from our own through multiple innate immune pathways,” said Price, Assistant Professor, Genome Regulation and Cell Signaling Program, Ellen and Ronald Caplan Cancer Center. 

At the heart of this work is RNA - the molecular signature that can reveal whether a cell is under attack. Viruses often generate double-stranded RNA, a key trigger for immune defence. However, human cells also produce small amounts of similar RNA, creating a complex challenge: how to detect genuine threats without causing harmful false alarms.

Price’s research focuses on how cells navigate this fine balance. By examining RNA structure, the proteins that bind to it, and subtle chemical modifications, his team aims to uncover how immune sensors distinguish viral RNA from the body’s own molecules with such precision.

Location plays a crucial role. Immune sensors that detect viral RNA operate primarily in the cytoplasm, while protective mechanisms within the nucleus help prevent the system from mistakenly targeting its own genetic material. Understanding how these spatial controls interact could provide new insight into immune regulation at a fundamental level.

The findings could have broad implications. A clearer picture of how immune recognition works may inform the development of more targeted antiviral therapies, as well as strategies to prevent inappropriate immune activation seen in inflammatory and autoimmune conditions.

By probing the molecular rules that govern immune sensing, this research aims to sharpen our understanding of how the body defends itself - without turning that defence inward.

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