Ebola virus nucleocapsid assembly revealed
At this moment, the world has few tools to combat deadly filoviruses, such as Ebola and Marburg viruses. The only approved vaccine and antibody treatments protect against just one filovirus species.
Scientists are working to guide the development of new antivirals by leading some clever enemy reconnaissance. These researchers use high-resolution imaging techniques to examine a virus's molecular structure—and uncover where a virus is vulnerable to new therapies.
In a new Cell study, scientists share the first detailed, complete images of a viral structure called the Ebola virus nucleocapsid. This breakthrough may accelerate the development of antivirals that target this viral structure to combat several filoviruses at once.
"A universal antiviral is the dream for stopping any kind of viral disease," says the first author of the Cell study. "This study brings us a step closer to finding a universal antiviral."
Ebola virus relies on its nucleocapsid structure to protect and replicate its own genetic material inside host cells—and suppress host cellular immunity. Thanks to the nucleocapsid, Ebola can turn infected host cells into virus-making factories.
For the study, the authors achieved a first in science—by harnessing an imaging technique called cryo-electron tomography, she glimpsed Ebola's nucleocapsid structure at work inside actual infected cells.
At first glance, the Ebola virus nucleocapsid looks like a coiled telephone cord. The authors revealed the stages of coiling and compression of the coil. They also discovered that the nucleocapsid's cylindrical shape is made up of three layers. Each layer plays a different role as the virus replicates in host cells. Before the imaging studies, the existence of the outer layer was entirely unknown.
The work also shows how this outer layer is composed, and how it provides a flexible tether between the nucleocapsid and the viral membrane.
"We found that the core protein adopts different forms in the distinct layers of the nucleocapsid to play different roles. ," says the study’s senior author.
Further investigations revealed how the proteins in these layers make contact with each other during assembly in host cells—and how the Ebola virus rearranges these proteins when nucleocapsids help form new viral particles.
As the author explains, targeting the nucleocapsid spells game over for the virus. "If you don't have a nucleocapsid, nothing can happen. That's the core of the virus," the author says.
In fact, the Ebola virus nucleocapsid plays such a critical role in infection that authors suspect the nucleocapsid's overall structure may have stayed the same as filoviruses evolved. Scientists call this kind of crucial structural feature "conserved" when it is shared across related species.
Indeed, all pathogenic filovirus species known so far, including Ebola and Marburg virus, share a conserved nucleocapsid structure, says the author.
