Research led by University of Toronto graduate student Jonathan Cook and his supervisor Dr. Jeffrey Lee, employing X-ray crystallography at the Canadian Light Source, has provided a better understanding of how infectious salmon anemia virus (ISAV) attaches to cells and infects. These results illuminate a potential pathway to developing a vaccine to protect salmon populations from the deadly virus.

Outbreaks of the devastating virus have periodically decimated farmed salmon operations in Canada’s East Coast, Chile, Scotland and Norway, and the virus has been found in wild salmon stocks as well. Despite its name, the virus is not isolated to salmon. Rainbow trout are also susceptible.

The virus has caused “one of the most economically destructive viral aquaculture pandemics in recent history, causing billions of dollars in economic losses in an increasing number of countries in the last 30 years,” according to the U of T researchers.

“No treatment is currently available, and vaccination efforts have only resulted in partial protection.”

Through crystallography, they were able to image the structure of a specific hemagglutinin-esterase (HE) protein to learn how it attaches itself within the fish’s respiratory system and then moves on to bind up red blood cells, causing the deadly anemia that gives the virus its name.

Cook says knowing how and where the protein attaches itself will be a key piece of information for vaccine developers to develop an antigen that will prevent the attachment process.

“A lot of the time what we as structural biologists do is we look for chinks in the armour, some weakness that we can target directly,” said Cook in an interview.

Dr. Lee holds the Canada Research Chair in Structural Virology and is an associate professor in the Department of Laboratory Medicine and Pathobiology at the U of T.  He and Cook were assisted in their search and data analysis by Dr. Azmiri Sultana. Their research paper into the salmon virus was recently published in the Proceedings of the National Academy of Sciences.

In an interview, Dr. Lee said his lab will continue to use the CLS crystallography beam lines, which he calls “a critical piece of infrastructure” for his lab to continue examining protein structures.

“We are still trying to figure out the precise mechanism of entry and fusion,” said Dr. Lee, explaining that ISAV is somewhat unique in that it has a two-component protein entry system, the HE and F proteins.

“We are interested in how these proteins interact and interplay to facilitate entry. It is a unique mechanism different than those seen in influenza, Ebola and HIV-1.”

Cook, Jonathan D., Azmiri Sultana, and Jeffrey E. Lee. "Structure of the infectious salmon anemia virus receptor complex illustrates a unique binding strategy for attachment." Proceedings of the National Academy of Sciences 114, no. 14 (2017): E2929-E2936. DOI: 10.1073/pnas.1617993114

Story by Murray Lyons

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