Scientists Discover How the Andes Hantavirus Enters Human Cells
Amul Info ·
A study published in Nature reveals how the Andes hantavirus binds to human cells and how antibodies can block this process. The findings could support the development of new treatments for hantavirus infections.
Scientists have discovered how the Andes hantavirus, found in South America, attaches to human cells and how antibodies capable of preventing infection block its activity. The findings, published in the scientific journal Nature, open up new possibilities for developing treatments against hantavirus infections.
Hantaviruses are a group of RNA-containing viruses that are spread primarily by rodents. People can become infected by inhaling dust contaminated with particles of urine, faeces or saliva from infected rodents.
Some hantavirus species are found mainly in Europe and Asia, while others occur in the Americas. Certain types cause haemorrhagic fever with kidney damage, whereas others can affect the lungs and heart. In severe cases, respiratory failure may develop and become life-threatening. At present, only a limited number of specifically approved antiviral medicines are available for treating hantavirus infections, so treatment is mainly focused on relieving symptoms.
An international research team led by Leandro Battini of Université Paris Cité in France investigated how the Andes hantavirus enters cells. One distinctive feature of this virus is that, unlike most other hantaviruses, it can be transmitted from person to person in certain circumstances.
To enter a human cell, the virus must first attach to its surface. The Andes hantavirus uses a protein called PCDH1, which is found on the surface of cells. This protein is also present in blood vessel cells, where it normally helps cells connect with one another. Although scientists already knew that the virus interacts with this protein, the precise way in which they bind had remained unclear.
The researchers produced a laboratory model of a protein spike on the virus’s surface and examined it alongside the PCDH1 receptor using cryo-electron microscopy. This technique allowed them to analyse the structures at very high resolution.
The results showed that four molecules of the viral protein Gn assemble to form a small pocket at the centre of the spike. A specific region of the PCDH1 protein fits into this pocket and interacts with all four Gn molecules simultaneously. This means that the structure required to recognise the receptor forms only when the viral protein spike is fully assembled. Another protein in the spike, Gc, helps the viral envelope fuse with the cell membrane.
The scientists also identified three small structural regions of the Gn protein that help the virus recognise human cells. During experiments, corresponding regions of another hantavirus, the Hantaan virus, were replaced with those from the Andes virus. The laboratory-produced viral particles then began binding to the PCDH1 receptor. However, the interaction was weaker than that observed with the original Andes virus.
Another important finding concerns how antibodies prevent the virus from attaching to cells. Because the pocket where the virus binds to the receptor is extremely narrow, ordinary antibodies have difficulty entering it directly. Nevertheless, the researchers found that antibodies can block the virus through two different mechanisms.
Two of the four neutralising antibodies studied attach near the pocket and cover its entrance. The other two bind to different regions of the viral protein spike. Their size prevents the PCDH1 receptor from approaching the site where binding would normally occur. In this way, antibodies can stop the virus from attaching to a cell without entering the pocket themselves.
According to the researchers, the discovery could be important for developing new treatments for hantavirus infections. One possible approach is to design small molecules or specialised antibodies capable of fitting into the pocket the virus uses to recognise its receptor. If this region can be blocked, the virus may find it more difficult to attach to cells and initiate infection.
However, further research is needed to determine how effective this approach could be as a treatment.