Writing today (Oct. 28, 2013) in the journal Virology, a team led by UW-Madison biochemistry Professor Ann Palmenberg provides a meticulous topographical model of the capsid or protein shell of a cold virus that until 2006 was unknown to science.
Rhinovirus C is believed to be responsible for up to half of all childhood colds, and is a serious complicating factor for respiratory conditions such as asthma. Together with rhinoviruses A and B, the recently discovered virus is responsible for millions of illnesses yearly at an estimated annual cost of more than $40 billion in the United States alone.
The work is important because it sculpts a highly detailed structural model of the virus, showing that the protein shell of the virus is distinct from those of other strains of cold viruses.
"The question we sought to answer was how is it different and what can we do about it? We found it is indeed quite different," says Palmenberg, noting that the new structure "explains most of the previous failures of drug trials against rhinovirus."
The A and B families of cold virus, including their three-dimensional structures, have long been known to science as they can easily be grown and studied in the lab. Rhinovirus C, on the other hand, resists culturing and escaped notice entirely until 2006 when "gene chips" and advanced gene sequencing revealed the virus had long been lurking in human cells alongside the more observable A and B virus strains.
The new cold virus model was built "in silico," drawing on advanced bioinformatics and the genetic sequences of 500 rhinovirus C genomes, which provided the three-dimensional coordinates of the viral capsid.
"It's a very high-resolution model," notes Palmenberg, whose group along with a team from the University of Maryland was the first to map the genomes for all known common cold virus strains in 2009. "We can see that it fits the data."
With a structure in hand, the likelihood that drugs can be designed to effectively thwart colds may be in the offing. Drugs that work well against the A and B strains of cold virus have been developed and advanced to clinical trials. However, their efficacy was blunted because they were built to take advantage of the surface features of the better known strains, whose structures were resolved years ago through X-ray crystallography, a well-established technique for obtaining the structures of critical molecules.
Because all three cold virus strains all contribute to the common cold, drug candidates failed as the surface features that permit rhinovirus C to dock with host cells and evade the immune system were unknown and different from those of rhinovirus A and B.
Based on the new structure, "we predict you'll have to make a C-specific drug," explains Holly A. Basta, the lead author of the study and a graduate student working with Palmenberg in the UW-Madison Institute for Molecular Virology. "All the [existing] drugs we tested did not work."
Antiviral drugs work by attaching to and modifying surface features of the virus. To be effective, a drug, like the right piece of a jigsaw puzzle, must fit and lock into the virus. The lack of a three-dimensional structure for rhinovirus C meant that the pharmaceutical companies designing cold-thwarting drugs were flying blind.
"It has a different receptor and a different receptor-binding platform," Palmenberg explains. "Because it's different, we have to go after it in a different way."
In addition to Basta and Palmenberg, co-authors of the new studies include Jean-Yves Sgro, Shamaila Ashraf, Yury Bochkov and James E. Gern, all of UW-Madison.
—Terry Devitt, 608-262-8282, email@example.com
The new rhinovirus C studies were supported by the National Institutes of Health, grants AI17331 and U19 AI104317.
NOTE: An image of the model can be downloaded at http://www.news.wisc.edu/newsphotos/coldVirus_13.html
Ann C. Palmenberg | EurekAlert!
Chances to treat childhood dementia
24.07.2017 | Julius-Maximilians-Universität Würzburg
World first: Massive thrombosis removed during early pregnancy
20.07.2017 | Universitätsspital Bern
3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects
A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...
Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.
For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...
What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.
To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...
The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....
A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...
21.07.2017 | Event News
19.07.2017 | Event News
12.07.2017 | Event News
24.07.2017 | Power and Electrical Engineering
24.07.2017 | Materials Sciences
24.07.2017 | Materials Sciences