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!
Cancer: Molecularly shutting down cancer cachexia
30.08.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Bringing artificial enzymes closer to nature
30.08.2016 | Universität Basel
Scientists and engineers striving to create the next machine-age marvel--whether it be a more aerodynamic rocket, a faster race car, or a higher-efficiency jet...
Waveguides are widely used for filtering, confining, guiding, coupling or splitting beams of visible light. However, creating waveguides that could do the same for X-rays has posed tremendous challenges in fabrication, so they are still only in an early stage of development.
In the latest issue of Acta Crystallographica Section A: Foundations and Advances , Sarah Hoffmann-Urlaub and Tim Salditt report the fabrication and testing of...
Electrochemists at TU Graz have managed to use monocrystalline semiconductor silicon as an active storage electrode in lithium batteries. This enables an integrated power supply to be made for microchips with a rechargeable battery.
Small electrical gadgets, such as mobile phones, tablets or notebooks, are indispensable accompaniments of everyday life. Integrated circuits in the interiors...
Recent findings indicating the possible discovery of a previously unknown subatomic particle may be evidence of a fifth fundamental force of nature, according...
A nanocrystalline material that rapidly makes white light out of blue light has been developed by KAUST researchers.
25.08.2016 | Event News
24.08.2016 | Event News
12.08.2016 | Event News
30.08.2016 | Ecology, The Environment and Conservation
30.08.2016 | Power and Electrical Engineering
30.08.2016 | Life Sciences