A*STAR scientists discover Switch to boost anti-viral response to fight infectious diseases

Scientists from Bioprocessing Technology Institute (BTI), Singapore under the Agency of Science, Technology and Research (A*STAR) have identified the molecular switch that directly triggers the bodys first line of defence against pathogens, more accurately known as the bodys innate immunity.


The scientists found that this switch called Brutons tyrosine kinase (BTK) when turned on, activates the production of interferons – a potent class of virus killers that enables the body to fight harmful pa-thogens such as dengue and influenza viruses.
While there are anti-viral drugs to treat influenza, the high rates of mutation that are characteristic of the influenza virus have made it difficult to treat with one universal drug or vaccine. As for dengue, there are currently no clinically approved vaccines or cures either. This discovery of BTKs role as a critical switch that boosts the bodys anti-viral response, paves the way for developing anti-viral drugs that target the BTK switch to fight infectious diseases.

To investigate the role of BTK in innate immunity, the research team from BTI extracted a class of in-nate immune cells known as macrophages from both normal mice and from mice deficient in BTK and challenged them with the dengue virus. They found that the BTK-deficient immune cells were unable to produce interferons, and hence had much higher viral counts compared to the healthy immune cells that had high-levels of interferons to fight the virus effectively.
To further demonstrate the critical role of BTK in anti-viral response, the team focused on BTKs role in Toll-like Receptor 3 (TLR3) signalling. TLR3 is needed for cells to activate the interferon response when cells are infected by viruses. The team examined the effect of having a perpetually-on or -off BTK switch in TLR3 signalling. They uncovered that a constitutively active or on BTK switch enhanced the production of interferon, resulting in a stronger and more lasting anti-viral response with significant reduction in Dengue viral counts. In contrast, a perpetually off BTK switch led to a poor anti-viral response with very low levels of inteferons produced, and little protection against Dengue virus infection.

Previously, scientists have always thought that BTK is important primarily in antibody production due to observations made of an inherited genetic disorder in humans called X-linked Agammaglobulinemia (XLA). These patients do not have a functional BTK switch, and are unable to produce antibodies because defects in BTK cripple maturation of B cells, a type of white blood cell that produces antibo-dies.


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