A long-standing belief that mammals use the same potent antiviral molecules deployed by plants and invertebrates is being challenged by researchers at Icahn School of Medicine at Mount Sinai.
Their findings, published in the July 10, 2014, issue of Cell Reports, surprised many scientists who assumed that antiviral RNA Interference (RNAi) exists in humans as a natural result of evolution.
Scientists know that human cells, like cells in every living organism with a nucleus, encode and generate small RNAs, which influence our genetics. It is also known that mammals combat viruses with interferons—proteins manufactured by immune cells in response to pathogens.
“If RNAi does exist in mammals, we can conclude that it is unlikely to play a physiological part in how we respond to infection,” says lead researcher Benjamin tenOever, PhD, Irene and Dr. Arthur M. Fishberg Professor in the Department of Microbiology at Icahn School of Medicine at Mount Sinai.
To determine whether any type of RNAi is an actor in the inhibition of viruses, Mount Sinai scientists administered mice with variations of a harmless virus incapable of causing disease in mammals. A version of the virus encoded with the ability to block the interferon response system gained strength, while another variant designed to fight any type of RNAi weakened immediately as a result.
The findings challenge two controversial studies that appeared in the journal Science in 2012, which suggested that mammals utilize RNAi in an antiviral fashion. This new research is expected to have an impact on drug discovery.
Scientists have hailed small RNAs in recent years because of the molecules’ ability to alter an individual’s genetics in any tissue where a gene is problematic. But researchers have been concerned that if small RNAs are part of humans’ viral response, then drugs that use them could indirectly harm patients’ immune systems.
“This finding that RNAi is not part of the interaction of the human host and viruses can be used to create novel therapeutics that express small RNAs to treat cancer and other illnesses,” says Peter Palese, PhD, Professor and Chair of Microbiology at Icahn School of Medicine at Mount Sinai.
Dr. tenOever says his close collaboration with teams at the Icahn Institute for Genomics and Multiscale Biology, and the Microbiology Department at Icahn School of Medicine at Mount Sinai, helped him advance his research. “Extraordinary claims such as antiviral RNAi in mammals require extraordinary proof,” says Dr. tenOever. “The strong infrastructure we have here at Mount Sinai allowed us to search for signs of this claim, but ultimately it demonstrated what we already knew—it is all about interferon.”