October 11, 2013
Researchers Discover Antiviral Response In Mammals Similar To That Found In Plants
Brett Smith for redOrbit.com - Your Universe Online
Previous research has shown that plants and invertebrates use an immune response called the RNA interference (RNAi) pathway to build a weapon against a viral infection.
Two new studies from scientists at the University of California, Riverside have found that a similar pathway exists in mammals, but it is typically suppressed by viral proteins. The study researchers said if this suppression could be lifted, it would open the door to a completely new way to treat a viral infection.
In the studies, the scientists were able to remove the suppressor protein from the virus. This allowed laboratory mice to quickly eliminate an infection from the Nodamura virus from their system using the RNAi process, which dispatches small interfering RNAs (siRNAs) to kill the disease.
"Many have tried to do this, that is, find the viral siRNAs in mammals, but they could not find the key," said study researcher Shou-Wei Ding, a microbiologist at UC Riverside. "The key was our prior knowledge of the B2 protein in the Nodamura virus, a virus few people know about. Other scientists asked me, 'What is the Nodamura virus?' They have been studying the more well-known human viruses, but Nodamura virus infection of mice proves to be the best model."
The foundation of the studies comes from Ding’s work in the late 1980s and 1990s at the Waite Institute in South Australia with the cucumber mosaic virus, a disease that infects over 1,000 plant species, including many major crops.
Using a computational analysis, Ding found a small gene he called 2b that he showed plays a vital role in spreading the virus within the host plant. After comparing his results to studies on the B2 protein of the insect-infecting Flock house virus, Ding theorized that 2b and B2 proteins act by suppressing the host's antiviral defense.
After moving in 1996 to the Institute of Molecular Agrobiology in Singapore, Ding and colleagues found that the 2b protein did in fact suppress the virus-fighting properties in plants. Ding’s research over the next decade with the Flock house virus eventually revealed that fruit flies and certain nematodes have the same RNAi virus-killing properties as plants, but the virus’ B2 protein stops their defenses from working. If the B2 was experimentally removed from the virus, the hosts were able to produce massive amounts of siRNAs and rapidly destroy the virus.
This revelation led Ding to another question – "If RNAi remains as an effective antiviral defense in plants, insects and nematodes after their independent evolution for hundred millions of years, why would it stop working with mammals?"
To find an answer, Ding decided to pursue similar research with the Nodamura virus—which kills young mice. In one of the published studies, the lab of Olivier Voinnet at the Swiss Federal Institute of Technology in Zurich worked with Ding to detect viral siRNAs in mouse embryonic stem cells infected by the Encephalomyocarditis virus, evidence of the antiviral pathway in mammals.
Ding said his next objective is to raise $5 million to work on new vaccines based on his previous research for human pathogens such as dengue fever.
"Maybe this is what we have been missing in knowing how humans combat viral infections," he said. "There are many different antiviral mechanisms in our bodies, but maybe RNAi functions as the most important antiviral defense mechanism. Maybe this is the one that really matters."
The two studies published in the journal Science are: "RNA Interference Functions as an Antiviral Immunity Mechanism in Mammals" and "Antiviral RNA Interference in Mammalian Cells."