Scientists have identified for the first time how the immune system uses an antibody to prevent hantavirus infection.
An image of the Puumala virus glycoprotein spike bound by neutralising antibody P-4G2. Image credit: Rissanen et al. (CC BY 4.0)
The findings, published today in eLife, may lead to new approaches to treat or prevent these infections.
Rodents in some parts of the world carry hantaviruses, which may be spread to humans through exposure to rodent excrement or saliva particles in the air. The viruses can cause haemorrhagic fevers and respiratory diseases of varying severity, depending on the virus species. In some cases, these infections can be serious or even fatal.
“As with the currently circulating coronavirus, spike proteins on the outside of hantaviruses help them to get inside human cells,” explains first author Ilona Rissanen, Postdoctoral Research Associate at the Institute of Biotechnology, University of Helsinki, Finland, and the Division of Structural Biology, University of Oxford, UK. “But antibodies created by the immune system can bind to the hantavirus spike proteins and prevent this from happening. We wanted to explore the molecular interactions that enable antibodies to neutralise hantaviruses in this way.”
To do this, Rissanen and colleagues studied a neutralising antibody elicited in bank voles – natural carriers of a hantavirus called Puumala virus – and looked at how it binds to the Puumala virus spike protein. They applied techniques called X-ray crystallography and electron cryo-microscopy to create the first detailed 3D images of the interaction.
The team suggests that the insights from this work will help scientists who are currently attempting to create therapeutics that can bind to the spike protein and stop the virus from infecting cells. The work may also be useful for the development of vaccines against existing and newly emerging hantaviruses.
“These viruses will continue to emerge, and in order to predict, control and manage future outbreaks, it is important to understand the structure of the viral components that are key to infection,” concludes senior author Thomas Bowden, Associate Professor at the Wellcome Centre for Human Genetics, University of Oxford. “Our study identifies a site of immune vulnerability on the hantavirus surface that is targeted by the immune system and may be exploited in future interventions.”
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