Defense Mechanism in Human Cells May Be Used to Fight Deadly Diseases
A defense mechanism by which plants and animals fight off RNA viruses was recently observed in human cells for the first time, offering researchers a look at new ways to treat viral diseases.
Outbreaks of the influenza, Ebola, West Nile, and Zika viruses have caused notable epidemics affecting the health of people around the world in recent years. Now, a research team from the University of California’s Riverside campus has released new findings identifying a virus-suppressing function in human cells that may be used to fight deadly diseases.
RNA viruses are a group of pathogens that cause some of the most dangerous and lethal diseases known to humans. The viruses contain RNA as their genetic material, and replicate their genomes to infect human hosts by exploiting the presence of RNA-dependent RNA polymerases. There are 938 known RNA viruses, and researchers have found these pathogens to be very adaptive with and have higher mutation rates than DNA viruses. Along with influenza, Ebola, West Nile, and Zika viruses, other well-known diseases in the RNA Virus Database include poliomyelitis, hepatitis C, and HIV.
In a recent study published in the journal Nature Microbiology, a team of researchers investigated the way RNA viral infections work in human cells. Study co-lead author Shou-Wei Ding, PhD, had previously researched the mechanisms in plant, insect, and mice cells that fight off certain viruses, known as RNA interference (RNAi). RNAi combats viral infections and stops the replication of pathogens by silencing the activity of viral genes. While RNA viruses have evolved over time to suppress and avoid RNAi, scientists have observed protective antibodies and immunological processes that continue to defend against pathogens such as influenza.
In the new study, the research team investigated whether a virus-fighting mechanism in plants, insects, and nematodes involving the production of anti-viral RNA, or siRNA, occurred in humans, and successfully identified the process in human cells. The production of siRNA in infected human cells is mediated by an enzyme called Dicer, which likely went unobserved in past research because the process is suppressed by the NS1 protein found in influenza A virus as well as proteins found in other viruses. “This opens up a new way to understand how humans respond to viral infections and develop new methods to control viral infections,” said Dr. Ding in a recent press release from UC Riverside.
The findings of this study mark the first time an RNAi response has been demonstrated in human and mouse cells infected with the influenza A virus, and has shown that cells infected with an influenza A mutant lacking NS1 were able to produce the molecular complexes needed for RNAi. “Our studies show that the antiviral function of RNAi is conserved in mammals against distinct RNA viruses, suggesting an immediate need to assess the role of antiviral RNAi in human infectious diseases caused by RNA viruses, including Ebola, West Nile, and Zika viruses,” said study author Kate Jeffrey, PhD.
In a press release from the study’s partner institute, Massachusetts General Hospital, Dr. Jeffrey explained the implications of the study’s findings and how research into the RNAi defense response can be applied to help humans fight deadly viruses. “We now need to assess more directly the role of antiviral RNAi in human infectious diseases caused by RNA viruses — which include Ebola, West Nile and Zika along with influenza – and how harnessing or boosting the antiviral RNAi response could be used to reduce the severity of these infections,” said Dr. Jeffrey. “Bringing the expertise of Dr. Ding’s team, which specializes in the RNAi biology of lower organisms, together with my group that specializes in mammalian immunology was a perfect match.”