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Publications of the Week

Spatio-Temporal Characterization of the Antiviral Activity of the XRN1-DCP1/2 Aggregation against Cytoplasmic RNA Viruses to Prevent Cell Death

By February 25, 2020No Comments

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This week we profile a recent publication in Cell Death & Differentiation from Dr. Chen Seng Ng (pictured, right)
in the laboratory of Dr. Honglin Luo (second from left) at the Centre for Heart Lung Innovation.

Can you provide a brief overview of your lab’s current research focus?

Our current focus mainly falls into the category of virus-host interaction. We use enteroviruses as the main model. Firstly, we are very keen in investigating enteroviruses’ genetics, life-cycle, and viral pathogenesis. The application of knowledge gained would allow us to identify possible targets for therapeutic interventions. Secondly, viral infection “tips-off” host’s alarm system, which is the host immune response. Cells have sensors that detect viral infections. One of these sensors, called RIG-I-like receptor, usually detects the presence of viral RNA and alarms the host’s immune system. Therefore, we are also very keen in understanding how enterovirus replicative intermediates, or any of its by-products, affects the host immune response, as well as how the virus-triggered immune response contributes to the progression of human diseases.

What is the significance of the findings in this publication?

By collaborating with Dr. Takashi Fujita, a world leading researcher in infection and immunity from Kyoto University of Japan, we identified a new cellular antiviral mechanism involving the host RNA degradation system. We demonstrate that the presence of viral RNA intermediates generated during viral replication can trigger the relocation of RNA degradation enzymes into the viral replication complexes, allowing the host RNases to degrade viral RNA and inhibit uncontrolled viral propagation. We were also able to identify the characteristics of viral RNA that trigger this antiviral system. Cytoplasmic RNA viruses, including the newly emerging SARS-CoV-2 that is causing the ongoing epidemic of coronavirus disease 2019 (COVID-19), represent a large and important group of pathogens that infect a wide range of hosts. We hope that our findings will shed an important light on understanding cellular alternative antiviral mechanisms, and thus offer therapeutic benefits against RNA viruses.

What are the next steps for this research?

While our current study has pinpointed the characteristics of viral RNA that can trigger the redistribution of host RNases into the replication complexes, there is still a piece missing from the puzzle. How do these host RNases know that viral RNA is present? There could be another component upstream of these RNases, which can sense these viral RNAs and transmit signal to the host RNases. The next crucial goal will be to identify the upstream or interacting components of these RNases. To do so will require a mass screening process.

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