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Publications of the Week

N-Terminomics TAILS Identifies Host Cell Substrates of Poliovirus and Coxsackievirus B3 3C Proteinases That Modulate Virus Infection

By March 5, 2018No Comments

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 This week we profile a recent publication in the Journal of Virology from Dr. Eric Jan
and Dr. Julienne Jagdeo (pictured) at the Life Sciences Institute

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

My lab is interested in uncovering the mechanisms by which RNA viruses can infect a host cell and take over and hijack the cellular machinery to promote infection. We are especially in understanding enterovirus infection such as poliovirus and coxsackievirus that cause human disease.

What is the significance of the findings in this publication?

RNA viruses typically encode a limited number of proteins, yet during infection, these viral proteins can interact host proteins and manipulate cellular pathways. This study focuses on one such protein, the viral protease, which is essential for cleaving and processing the viral polyprotein into individual mature proteins. However, it is now apparent that enterovirus proteases also target and cleave host proteins. In this study, we have used an unbiased proteomics approaches called TAILS, developed by Dr. Chris Overall (UBC), to identify new host target proteins (~100) of the poliovirus and coxsackievirus 3C protease. We showed that a subset of these target proteins are important for infection. The identification of these new host targets reveal new insights into the cellular proteins and pathways that are directly targeted by viral proteases and shedding light into the fundamental host virus interactions that facilitate enterovirus infection.

What are the next steps for this research?

The next step is to delve deeper into the relevance of cleavage of these host target proteins. It is likely that some of these host target proteins may not be essential for virus infection but we believe that some are strategic for cleavage for promoting enterovirus infection. Indeed, in our study, we showed that expression of a cleavage-resistant mutant protein, p115, decreased viral yield, thus demonstrating that cleavage of this one protein is important for infection. The next goal is to understanding exactly why this p115 (and other strategic targets) are cleaved, possibly to inactivate the function of this protein/cellular pathway or possibly cleavage of the protein leads to a stable cleaved fragment protein that functions in virus infection. This latter point is very exciting as it suggests that the viral protease is actively cleaving a protein to create a truncated protein that may have novel function.

This research was funded by:

We are funded by both NSERC and CIHR.

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