By Danny Brown
A research team at Cardiff University’s School of Medicine have used a combination of X-ray crystallography and computer simulation to investigate in incredible depth how viruses bind to cells and cause infection. This insight could advance the exploitation of viruses for medical treatments and also help in the development of drugs and treatments for infections.
X-ray crystallography is the technique used to look at the atomic structure of molecules and crystals, where the beam of incident x-rays get deflected in many specific directions. By measuring the angles and intensities of the refracted x-rays, it is possible to create a three dimensional picture of the structure of electrons in the sample.
Alex Baker, one of the authors of the study, said: “We were interested in developing viruses for therapeutic applications, such as treating cancers, and for vaccine applications.
“We focussed on two specific viruses, called Ad26 and Ad48. These viruses are in clinical trials where they are showing promise as vaccines to protect against Ebola virus and HIV infection. We wanted to know more about how these viruses work as vaccines.”
The process the team took included making very pure samples of the virus proteins that bind the virus to the cell, infecting the cell. They made crystals out of the purified protein allowing them to perform the x-ray crystallography studies.
Baker went on to say: “We were able to investigate exactly how the viruses attach to proteins on the cell surface and we were surprised to find that they could not bind to a protein called CD46, which had previously been reported as the main virus receptor. Instead, we show that these viruses can bind weakly to a different entry receptor, called CAR. In so doing we identified a previously undiscovered mechanism that adenoviruses use to adjust their attachment to CAR.”
The study provided details of the basic biology of the viruses they were manipulating at a molecular level. Dr Alan Parker, senior author of the study said: “This study is important since it provides molecular level detail about the basic biology of the viruses we are manipulating. This information will help determine what the best antivirals might be to treat outbreaks of these viruses in their natural, disease causing state, but will also help progress their development for therapeutic purposes in the future.”
The study was funded by Tenovus Cancer Care, Cancer Research UK and Cancer Research Wales and was published in the journal, Nature Communications. There were also collaborators to the study based at Oxford and the Icahn School of Medicine at Mount Sinai in New York.