The manufacturer of Sovaldi, a Hepatitis C virus cure, has made over $10.3 billion. Other cures may someday be possible, thanks to a list of 99 new human cell and virus interactions discovered by Gladstone Institute's Holly Ramage.
“The biggest problem is delivering that sort of reagent into the human body,” Ramage, who published her findings in a January issue of Molecular Cell, pointed out. “And for some of these factors, we don’t have a really good idea of what they even do.”
There’s a chance the Hepatitis C virus, affecting 3.2 million according to CDC estimates, could become resistant to Sovaldi, and if it does, scientists want to be ready with drugs understanding what the virus does inside the body.
The human body is made up of cells, building blocks mostly too small for an unaided human eye to see. A University of California San Francisco lab recently modeled interactions between HIV and proteins inside cells, by combining biology and computer science.
Ramage heard the results and teamed with the lab to try the same method on Hepatitis C, back in November 2010. “The way the data was analyzed, there were a lot of choices,” she recollected. “It was really collaborative.”
The team needed to see how the virus affects cells, but healthy cells in the human body have a biological clock that orders them to stop growing. The team pumped cancer cells with the virus because they don’t have this clock.
The team went fishing: they cast chemically tagged 10 virus baits into cell soup, retrieving 133 cancer and interlocked virus proteins. When the virus reached certain host proteins, it attached itself; mysteriously wrecking havoc and copying so it didn’t die out.
The team ran electricity through the soup, separating proteins that responded differently, and held the virus-host protein pairs together with gel. Next, they placed the pairs inside a membrane - a gooey container - and colored the tagged virus proteins with more chemicals.
The team grabbed a mass spectrometry machine, which bombed the soup with tiny electrons and measured how many proteins were around. Once they matched the spikes in a graph to a list of known proteins, the final step was figuring out figuring out which proteins helped or hurt the virus.
Day by day, the team turned off host proteins and decided whether the virus grew stronger or weaker. They eventually found 139 virus and cell interactions that made a noticeable impact.
99 of the final proteins hadn’t been seen interacting before.
“It’s a nice paper, but it doesn’t mean it’s such a milestone, because it’s really experimental data,” Dr. Chen Liu, lead Hepatitis C researcher and associate chair of the University of Florida Department of Pathology said. “The relevance of the finding must be confirmed by the actual infection in the context of the patient population.”
Ramage, now at University of Pennsylvania, continues to study these host proteins and their interactions. “The first step would be to figure out what their normal function is and what their role is in the infection,” she said.
Originally published March 19 at http://abstractday.blogspot.com/2015/03/hepatitis-c-research-continues-even.html