The virus Hantaan belonging to the Hantaviridae family (Bunyavirales order) is a strain of non-vaccine preventable virus transmitted by rats and mice. It can give rise to fatal hemorrhagic fevers with renal syndrome and is in the same family as the deadly virus Sin Nombre; which has been linked to severe pulmonary illnesses with up to 40% fatality rate. Their treatment is also not yet available. Hantavirus RNA genome hides in nucleocapsids to evade being detected by the human immune system so the body cannot destroy it. The nucleocapsids should, therefore, be expected to be antiviral drugs target. However, little is known about this nucleocapsid which enables reading and copying of the genetic code by the viral polymerase as well as protects the genome.
Université Grenoble Alpes scientists: Benoît Arragain, Dr. Ambroise Desfosses, Dr. Irina Gutsche, Dr. Guy Schoehn and Dr. Hélène Malet from Electron Microscopy and Methods Group together with Dr. Juan Reguera from Aix-Marseille University worked on unraveling the 3D structure of the mystery of the recombinant metastable helical nucleocapsid of the Hantaan virus using the state-of-the art cryo-electron microscopes present in the Structural Biology Institute platform (IBS, Grenoble) and the European Synchrotron Radiation Facility (ERSF, Grenoble). Electron microscopy coupled with image processing enabled to visualize at high resolution the nucleocapsid, thereby deciphering the interactions that stabilize its helical structure. It reveals the position of a continuous groove that protects the RNA genome. The work is published in the peer-reviewed journal, eLife.
From the study, the authors were able to determine the structure of the nucleocapsid of the virus Hantaan as a 3.6 subunits per turn left-handed helix, with some of its residue not following the helical symmetry. Some portions of the nucleoprotein residues corresponding to a flexibly-linked coiled coil were found to not be necessary before helical stabilization could occur. Due to the myriad of interactions between its protomers, the nucleocapsid of the recombinant Hantaan virus can be stable under various types of temperature conditions as well as varying pH and salt levels. To further identify the importance of the structure of the nucleocapsid of the Hantaan virus, the study showed that it is compatible with the binding of long viral RNA.
Arragain and colleagues’ study has been able to show the importance of carrying out a structural determination of a viral nucleocapsid as it provides information at high resolution which is beyond scratching the surface. This study employed the cloning, expression, and purification of the nucleoproteins as well as the limited proteolysis of the nucleocapsid, image processing and the modeling of the RNA based on the La Crosse virus nucleoprotein.
Their study, which has provided evidence into how the structure of the nucleocapsid of the Hantaan virus is biologically pertinent and how they are similar to the helical nucleocapsids observed in other viral particles will advance future studies on the development of antivirals strong enough to defeat infections that arise as a result of the Hantaan virus.
Arragain, B., Reguera, J., Desfosses, A., Gutsche, I., Schoehn, G., and Malet, H. High resolution cryo-EM structure of the helical RNA-bound Hantaan virus nucleocapsid reveals its assembly mechanisms, eLife (2019) 8:e43075Go To eLife