"When a plant recognizes viral material, it creates a small inhibitory RNA (siRNA) that latches on to the virus and cleaves it," says Dr. tenOever. Human cells also have small RNAs in the form of miRNAs, but they are used to maintain cell health not to fight a virus. Drs. tenOever and Garcia-Sastre along with scientists from the University of Maryland's Department of Veterinary Medicine discovered that if they alter a viral genome by adding a binding site for a miRNA found in human cells, that molecule morphs into a plant-like attacker. It latches on to the virus and destroys it in the same way plant siRNAs do.
In this study, the scientists discovered a specific miRNA (miR-192) that is found in human and mouse lung cells, but not in the lungs of ferrets. They added multiple binding sites for miR-192 on to the H5N1 genome, and demonstrated in mice that, upon contact, lung cells destroyed the virus. They then demonstrated that H5N1 transmission between ferrets was not decreased when altered virus was used. The researchers also showed the approach works with other influenza A viruses.
"It is clear that we can apply this technology to any virus," Dr. tenOever says. "The only requirements are that we need a miRNA that is present in humans, but not in the model system where we want to study the virus, such as in ferrets. We also need a viral genome that permits insertion of miRNA target sites."
And once a virus is altered to contain the miRNA target sites, it can replicate ad infinitum for research in laboratories worldwide, Dr. tenOever says. "There is no need to continually go back to the drawing board," he says.
In January, a handful of scientists in nine nations
|Contact: Mount Sinai Press Office|
The Mount Sinai Hospital / Mount Sinai School of Medicine