Two studies published in Nature Communications discovered the structure of the Epstein-Barr virus and bacteriophage T7 portal. Currently there is no treatment for infections caused by this virus that, in addition to causing mononucleosis, causes several types of cancer.
Experts from the Biomedical Research Institute (IRB Barcelona) and the Molecular Biology Institute of Barcelona (IBMB-CSIC) described the structure of an essential protein for the Epstein-Barr virus infection process, known as portal.
The Epstein-Barr virus, belonging to the family of herpesviruses, is one of the most common human viruses and the leading cause of infectious mononucleosis (called the kissing disease), and also causes various cancers such as Burkitt and Hodgkins lymphomas, gastric cancer and nasopharyngeal cancer, as well as several autoimmune diseases. There is currently no treatment for infections caused by this virus.
“Knowing the structure of the portal protein could be useful for the design of inhibitors that can be used for the treatment of herpesvirus infections, such as Epstein-Barr. In addition, being an exclusive herpesvirus protein, these inhibitors would be specific against the virus and perhaps less toxic to humans,” says Miquel Coll, head of the Laboratory of Structural Biology of Complexes of Proteins and Nucleic Acids and Molecular Machines of IRB Barcleona and professor of the CSIC.
All herpesviruses have a similar infection system: once they enter the cellular interior and reach the nucleus, the viruses release their DNA, which can hide latent for years until, under certain circumstances, their multiplication is triggered.
The DNA is replicated and subsequently introduced into new viral capsids, to form new viruses that will attack other cells. The portal protein is the channel through which DNA enters the capsid of the virus and where it leaves when it infects cells.
In a second paper published recently in the same journal, researchers have also characterized the structure of the portal protein in bacteriophage T7. The bacteriophage T7 is a virus that exclusively infects bacteria and, interestingly, uses a system very similar to that of herpesviruses for the packaging of its DNA.
“Thanks to the structure of the bacteriophage T7 portal protein, we have been able to infer how Epstein-Barr’s would work,” explains Cristina Machón and Montserrat Fàbrega, postdoctoral researchers at IRB Barcelona and IBMB-CSIC and first author, along with Ana Cuervo, from the National Center of Biotechnology (CNB-CSIC), of the published works.
“In both viruses, the portal protein is composed of 12 subunits, forming a large mushroom-shaped structure, with a central channel through which the DNA passes. This channel has a valve that regulates the entry and exit of the genetic material of the virus,” explains Coll.
To study the structure of this protein, the researchers used both synchrotron X-ray diffraction techniques and high resolution electronic cryomicroscopy. Both studies were carried out in collaboration with the CNB-CSIC and the University of Oxford (United Kingdom).