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Publications of the Week

Coxsackievirus B3 Targets TFEB to Disrupt Lysosomal Function

By March 22, 2021No Comments

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This week we profile a recent publication in Autophagy from
Yasir Mohamud (pictured, right), Hui Tang (left), and Dr. Honglin Luo at UBC.

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

The Luo Laboratory studies mechanisms of viral pathogenesis with a particular focus on heart disease and neurodegeneration while also investigating strategies to leverage oncolytic virus for cancer therapy. As common human pathogens, enteroviruses (EVs) are responsible for ~1 billion global infections annually, with severe health outcomes manifesting in the vulnerable populations including infants, the elderly, and the immune-compromised. Recent evidence shows that EVs can hijack the host autophagy pathway for effective viral replication leading to cardiovascular and neurological disorders; however, the underlying mechanisms remain poorly defined. The focus of this project is to elucidate the molecular mechanism by which EVs subvert the host autophagy pathway.

What is the significance of the findings in this publication? 

The recent publication by Mohamud et al. demonstrates that Coxsackievirus B3 (CVB3, an EV) can disrupt the function of an important cellular organelle called the lysosomes. Lysosomes have traditionally been considered the disposal chamber of the cell but these versatile organelles have been shown to do much more including roles in active signaling, energy metabolism, and cellular repair. Our study identified a key transcription factor called TFEB, as a master regulator of lysosome function, as a novel target of CVB3. This finding provides new insights into how viruses subvert the host-antiviral machinery with potential implications for EV-induced pathogenesis.   

What are the next steps for this research? 

The ongoing/future aims of this project are to (1) develop anti-viral inhibitors based on the mechanism identified in cells that prevent EV-mediated disruption of autophagy; and (2) evaluate the safety and efficacy of candidate inhibitors in pre-clinical models. 

This work was funded by:

This research is supported by the Canadian Institutes of Health Research (PJT-173318 and PJT 159546) to Honglin Luo (Senior author). The first author (Yasir Mohamud) is supported by four-year PhD fellowship from University of British Columbia and Doctoral Fellowship from ALS Canada-Brain Canada.

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