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Viral Sensor Complex Activates Immune Response During Viral Infection

A research study by University of Texas researchers has identified a unique sensor that is essential for immune response activation during viral infection. This study gives a better insight into the intricate and overlapping mechanisms used by immune cells to resist infection.

Dr. Yong-Jun Liu and co-workers from University of Texas MD Anderson Cancer Center isolated and characterized proteins bound to a s.

ynthetic ds viral RNA known as poly I:C. Inside the myeloid dendritic cells, the researchers identified two known dsRNA sensors and a new viral sensor complex having three RNA helicases, DDX1, DDX21 and DHX36, and an adaptor molecule called TRIF. Myeloid dendritic cells play a significant role in detection of pathogens. The multi-helicase-TRIF complex can bind to poly I:C directly and thus kick start an immune response. Dr. Liu and his team ultimately showed that the DDX1 helicase directly bound to viral RNA whereas the other two helicases functioned as bridges to TRIF. The team also found that all the four components were necessary for a proper immune response. Significantly, any interference with the viral sensor complex hindered immune response to a type of rotavirus and influenza A infections.

Viruses contain nucleic acid (DNA or RNA) and a protective coating made of protein and they utilize host cell mechanisms to replicate. The body’s immune system can sense viral nucleic acids during viral infection, which leads to type 1 interferon (IFN) response activation. This response can affect viral replication.

Dr. Liu said that this study fills the gap in the understanding of the binding of receptors to nucleic acids and existence of other receptors or coreceptors, which will help the design of more effective antiviral medicines. He added that their study shows that the DDX1-DDX21-DHX36 complex stands for the missing poly I:C sensor and may be initiator of IFN production, which activates other known dsRNA sensors, thus amplifying the IFN response.

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