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!
Getting a grip on slippery cell membranes
28.06.2016 | Worcester Polytechnic Institute
Unexpected flexibility found in odorant molecules
27.06.2016 | Max-Planck-Institut für Struktur und Dynamik der Materie
R2D2, a joint project to analyze and development high-TRL processes and technologies for manufacture of flexible organic light-emitting diodes (OLEDs) funded by the German Federal Ministry of Education and Research (BMBF) has been successfully completed.
In contrast to point light sources like LEDs made of inorganic semiconductor crystals, organic light-emitting diodes (OLEDs) are light-emitting surfaces. Their...
High resolution rotational spectroscopy reveals an unprecedented number of conformations of an odorant molecule – a new world record!
In a recent publication in the journal Physical Chemistry Chemical Physics, researchers from the Max Planck Institute for the Structure and Dynamics of Matter...
Strands of cow cartilage substitute for ink in a 3D bioprinting process that may one day create cartilage patches for worn out joints, according to a team of engineers. "Our goal is to create tissue that can be used to replace large amounts of worn out tissue or design patches," said Ibrahim T. Ozbolat, associate professor of engineering science and mechanics. "Those who have osteoarthritis in their joints suffer a lot. We need a new alternative treatment for this."
Cartilage is a good tissue to target for scale-up bioprinting because it is made up of only one cell type and has no blood vessels within the tissue. It is...
Physicists in Innsbruck have realized the first quantum simulation of lattice gauge theories, building a bridge between high-energy theory and atomic physics. In the journal Nature, Rainer Blatt‘s and Peter Zoller’s research teams describe how they simulated the creation of elementary particle pairs out of the vacuum by using a quantum computer.
Elementary particles are the fundamental buildings blocks of matter, and their properties are described by the Standard Model of particle physics. The...
A year and a half on the outer wall of the International Space Station ISS in altitude of 400 kilometers is a real challenge. Whether a primordial bacterium...
09.06.2016 | Event News
24.05.2016 | Event News
20.05.2016 | Event News
28.06.2016 | Physics and Astronomy
28.06.2016 | Earth Sciences
28.06.2016 | Earth Sciences