Hantavirus particles in ‘open’ and ‘closed’ conformations in an aerosol. Image credit: Bertsy Goic, DrawInScience (CC BY 4.0)
Hantaviruses infect rodents and other small mammals, but do not harm them. When transmitted to humans, often through rodent urine, feces or saliva, they can cause serious and even fatal diseases. Currently, there are no known methods that effectively prevent hantavirus infections or treat the diseases that they cause.
During an infection, viruses invade the cells of their host. A hantavirus interacts with target cells through proteins on its surface called Gn and Gc glycoproteins. Previous work has shown that these glycoproteins are organized in bundles of four Gn and four Gc proteins, termed spikes, which project from the membrane that surrounds the virus. The Gc protein changes shape when it is activated and exposes a hidden region that can insert into the membrane of the target cell. The Gc proteins then change shape again to force the cell to fuse with the viral membrane. This process allows the virus to be taken up into the cell, where it can replicate.
While the structures of each viral glycoprotein have been determined in isolation, it was not known how they interact within the Gn/Gc spike. Such information is crucial to understand how the viruses infect cells and which areas are exposed to the immune system of the host – and so could be targeted by antiviral treatments.
Bignon et al. have now identified the molecular contacts that occur between spikes and interconnect them into a grid-like lattice on the surface of the virus. Genetically altering specific sections of the Gc glycoprotein strengthened or weakened these contacts, which correspondingly increased or decreased how stable the spike was. Preventing the contacts from forming resulted in cells releasing fewer virus-like particles.
Bignon et al. also show that at the body temperature of mammals, the shape of the spike fluctuates between an ‘open’ form that exposes the region of Gc that inserts into the cell membrane, and a ‘closed’ form that hides this region. However, when Gc is activated, the open form becomes unable to cause the viral and cell membranes to fuse together.
Together, the results presented by Bignon et al. help us to understand how changes to the hantavirus surface enable the virus to infect cells. This knowledge will help researchers to design vaccines that protect against hantavirus infections.
