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Publications of the Week

Enteroviral Infection Inhibits Autophagic Flux via Disruption of the SNARE Complex to Enhance Viral Replication

By April 4, 2018April 5th, 2018No Comments

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 This week we profile a recent publication in Cell Reports from Dr. Honglin Luo (third from right)
and Yasir Mohamud (third from left) at the Centre for Heart Lung Innovation at St. Paul’s Hospital

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

Our lab studies how enteroviruses, a very common human pathogen, initiate and/or promote disease progression with a particular focus on heart and neurodegenerative diseases. We are interested in understanding how enteroviruses infect and hijack the host cellular machinery, in particular the protein quality control system, which includes molecular chaperones and protein degradation pathways. Our ultimate goal is to use this knowledge to develop effective molecular therapeutics.

 What is the significance of the findings in this publication?

Enteroviruses are responsible for an estimated 1 billion global infections per year. For most adults, these infections are asymptomatic, however for infants, young children, and those with compromised immunity, enteroviruses pose a significant health threat, leading to heart failure-induced sudden death and infections of the central nervous system. Currently, there are no effective treatments against these medically important viruses.

The importance of abnormal protein aggregation in enterovirus-induced pathogenesis has been increasingly recognized; however, the underlying mechanisms are largely unclear. Working in parallel with Dr. William Jackson and colleagues at the University of Maryland, we identified a novel mechanism by which enteroviruses disrupt the normal process of autophagy (a “self-digestion” machinery), leading to the accumulation of toxic/misfolded proteins and organelles. Our findings also shed light on a previously unknown enteroviruses strategy that hijacks the autophagy pathway to promote their own growth.

 What are the next steps for this research?

Our next step is to develop autophagy-based chemical inhibitors for the treatment of enterovirus-induced infection of the heart and the central nervous system.

This research was funded by:

This work was supported by the Natural Sciences and Engineering Research Council, the ALS Canada, and the Heart & Stroke Foundation of Canada. The first author (YM) is supported by a four-year PhD fellowship from the University of British Columbia.

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