Researchers discover long sought after mechanism in human cells that could help treat diseases caused by viruses, including influenza and Ebola
A team of researchers, co-led by a University of California, Riverside professor, has found a long-sought-after mechanism in human cells that creates immunity to influenza A virus, which causes annual seasonal epidemics and occasional pandemics.
The research, outlined in a paper published online today in the journal Nature Microbiology, could have broad implications on the immunological understanding of human diseases caused by RNA viruses including influenza, Ebola, West Nile, and Zika viruses.
“This opens up a new way to understand how humans respond to viral infections and develop new methods to control viral infections,” said Shou-Wei Ding, a professor of plant pathology and microbiology at UC Riverside, who is the co-corresponding author of the paper.
The findings build on more than 20 years of research by Ding on antiviral RNA interference (RNAi), which involves an organism producing small interfering RNAs (siRNAs) to clear a virus.
His initial research showed that RNAi is a common antiviral defense in plants, insects and nematodes and that viral infections in these organisms require active suppression of RNAi by specific viral proteins. That work led him to study RNAi as an antiviral defense in mammals.
In a 2013 paper in the journal Science he outlined findings that show mice use RNAi to destroy viruses. But, it remained an open debate as to whether the same was true in humans.
That open debate led Ding back to a key 2004 paper in which he described a new activity of a protein (non-structural protein 1, or NS1) in the influenza virus that can block the antiviral function of RNAi in fruit flies, a common model system used by scientists.
In the current Nature Microbiology paper, the researchers demonstrated that human cells produce abundant siRNAs to target the influenza A virus when the viral NS1 is not active.
They showed that the creation of viral siRNAs in infected human cells is mediated by an enzyme known as Dicer and is potently suppressed by both the NS1 protein of influenza A virus and a protein (virion protein 35, or VP35) found in Ebola and Marburg viruses.
The researchers in the lab of the co-corresponding author, Kate L. Jeffrey, an investigator in the Massachusetts General Hospital gastrointestinal unit and an assistant professor of medicine at Harvard Medical School, further demonstrated that the infections of mature mammal cells by influenza A virus and other RNA viruses are inhibited naturally by RNAi, using mice cells specifically defective in 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,” Jeffrey said.
The Nature Microbiology paper is called “Induction and suppression of antiviral RNA interference by influenza A virus in mammalian cells.”
Scientists at The University of Texas at Austin have developed a new method to rapidly detect a single virus in urine, as reported this week in the journalProceedings of the National Academy of Sciences.
Although the technique presently works on just one virus, scientists say it could be adapted to detect a range of viruses that plague humans including Ebola, Zika and HIV.
“The ultimate goal is to build a cheap, easy-to-use device to take into the field and measure the presence of a virus like Ebola in people on the spot,” says Jeffrey Dick, a chemistry graduate student and co-lead author of the study. “While we are still pretty far from this, this work is a leap in the right direction.”
The other co-lead author is Adam Hilterbrand, a microbiology graduate student.
The new method is highly specific, meaning it is only sensitive to one type of virus, filtering out possible false negatives caused by other viruses or contaminants.
There are two other commonly used methods for detecting viruses in biological samples, but they have drawbacks. One requires a much higher concentration of viruses, and the other requires samples to be purified to remove contaminants. The new method, however, can be used with urine straight from a person or animal.
Hybrid device integrates a microfluidic chip for sample preparation and an optofluidic chip for optical detection of individual molecules of viral RNA A team led by researchers at UC Santa Cruz has developed chip-based technology for reliable detection of Ebola virus and other viral pathogens.
The current gold standard for Ebola virus detection relies on a method called polymerase chain reaction to amplify the virus’s genetic material for detection.
“We’re detecting the nucleic acids directly, and we achieve a comparable limit of detection to PCR and excellent specificity.” In laboratory tests, the system provided sensitive detection of Ebola virus while giving no positive counts in tests with two related viruses, Sudan virus and Marburg virus.
The system combines two small chips, a microfluidic chip for sample preparation and an optofluidic chip for optical detection.