Scientists at The University of Texas at Austin have discovered that a protein produced by the influenza A virus helps it outwit one of our body's natural defense mechanisms. That makes the protein a potentially good target for antiviral drugs directed against the influenza A virus.
Better antiviral drugs could help the millions of people annually infected by flu, which kills up to 500,000 people each year.
This region of the NS1 viral protein binds the host protein DDX21, making it a potential target for new antivirals against the influenza virus
When an influenza virus infects a human cell, it uses some of the host's cellular machinery to make copies of itself, or replicate. In this study, the researchers discovered that a protein produced by human body cells, DDX21, blocks this replication process. They also discovered that a protein created by the virus, NS1, in turn blocks DDX21 and promotes viral replication.
"If you could figure out how to stop NS1 from binding to DDX21, you could stop the virus cold," said Robert Krug, a professor in the College of Natural Sciences at The University of Texas at Austin and corresponding author on the study, which appears today in the journal Cell Host and Microbe.
Krug said that in addition to countering the body's defense mechanisms, the viral NS1 protein actually performs other important roles for the virus, such as inhibiting the host's synthesis of interferon, a key antiviral protein.
"It means that if you could block that NS1 function, you'd be blocking not only its interaction with DDX21 but many other important functions, so it's a great target," said Krug.
The need for new antiviral drugs against the influenza virus is great. Because flu vaccines are not 100 percent effective, antiviral drugs play an important role in fast-spreading epidemics. Yet influenza A viruses are developing resistance to antiviral drugs currently in use.
Krug and his team discovered that the viral NS1 protein is often associated, or bound together, with the host DDX21 protein in infected human body cells. To understand what role DDX21 might play in virus replication, the researchers used a technique called siRNA gene silencing to knock down the production of DDX21 in infected cells. When they did, virus replication increased 30 fold.
"That told us that DDX21 is a host restriction factor, that it inhibits replication," said Krug. "That was the key to understanding what was happening. It was an exciting moment."
Next, the researchers discovered that DDX21 blocks replication by binding to a protein that the virus needs to replicate, called PB1. Finally, they discovered that NS1 binds to DDX21 and makes PB1 available again for replication. This result confirmed that NS1 was indeed the countermeasure used by the virus to get around the body's natural defense mechanism.
Krug's co-authors are Guifang Chen, Chien-Hung Liu and Ligang Zhou, all from The University of Texas at Austin.
Support for this research was provided by a grant from the National Institutes of Health.
Marc Airhart | Eurek Alert!
More than just a mechanical barrier – epithelial cells actively combat the flu virus
04.05.2016 | Helmholtz-Zentrum für Infektionsforschung
Discovery of a fundamental limit to the evolution of the genetic code
03.05.2016 | Institute for Research in Biomedicine (IRB Barcelona)
Using an ultra fast-scanning atomic force microscope, a team of researchers from the University of Basel has filmed “living” nuclear pore complexes at work for the first time. Nuclear pores are molecular machines that control the traffic entering or exiting the cell nucleus. In their article published in Nature Nanotechnology, the researchers explain how the passage of unwanted molecules is prevented by rapidly moving molecular “tentacles” inside the pore.
Using high-speed AFM, Roderick Lim, Argovia Professor at the Biozentrum and the Swiss Nanoscience Institute of the University of Basel, has not only directly...
If a person pushes a broken-down car alone, there is a certain effect. If another person helps, the result is the sum of their efforts. If two micro-particles are pushing another microparticle, however, the resulting effect may not necessarily be the sum their efforts. A recent study published in Nature Communications, measured this odd effect that scientists call “many body.”
In the microscopic world, where the modern miniaturized machines at the new frontiers of technology operate, as long as we are in the presence of two...
Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.
Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...
Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.
In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...
Honeycomb structures as the basic building block for industrial applications presented using holo pyramid
Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...
27.04.2016 | Event News
15.04.2016 | Event News
12.04.2016 | Event News
04.05.2016 | Materials Sciences
04.05.2016 | Physics and Astronomy
04.05.2016 | Physics and Astronomy