Read the full edition No. 26 of the Health newspaper

No treatment has succeeded in eradicating hepatitis C from the world. The disease leads to 300,000 deaths every year, and is one of the main causes of liver cancer.

In new research, recently published in the journal Nature, a team of Danish scientists shows how two coat proteins come together. The molecular arrangement of these proteins allows them to capture cells and avoid detection by neutralizing antibodies. Although the structure of the protein is different, it works similarly to the spike protein of the coronavirus in entering and infecting human cells.

This decision has major implications for how hepatitis C vaccine development is approached.

“We are the first to identify the protein complex on the surface of the hepatitis C virus that allows it to bind to our cells,” said Jannick Prentø, lead author of the study and associate professor at the University of Copenhagen.

“This knowledge of the structure of the complex protein allows us to design vaccine candidates that prevent the virus from entering cells,” said Elias Augestad, a postdoctoral fellow at the University of Copenhagen and co- the study’s senior author.

Understanding the protein complex and how the hepatitis C virus affects cells is the final key step in vaccine design.

Ideally, the proposed vaccine would train the immune system to recognize the hepatitis C protein complex, prompting the release of neutralizing antibodies. These antibodies would then bind to the protein complex, making it unable to bind and infect cells.

“It is extremely difficult to express and remove the protein complex, which is why it has not been done before. The structure of these proteins on the surface of the hepatitis C virus makes them very vulnerable,” explained Prentø.

Researchers did not know what they were dealing with, so when someone tried to reproduce these protein structures in the laboratory, they fell apart before they had a chance to study them.

According to the authors, replication and analysis of protein complexes from hepatitis C viruses is necessary for the development of vaccines. Because scientists now better understand the structure that makes the hepatitis C virus so infectious, the hope of a vaccine is closer than ever.

Research summary

The researchers studied the structure of the proteins on the surface of the hepatitis C virus (HCV). They used a special microscope called a cryo-electron microscope to get very detailed images of these proteins. To do this, they first needed to make and purify the proteins in the laboratory. Then they quickly froze the proteins and took pictures of them. Using computers, they combined these images to create a 3D model of the proteins.

Main results

The study showed that HCV surface proteins, called E1 and E2, form pairs which then join together in pairs. This structure helps explain how the virus avoids detection by the body’s immune system. The researchers also discovered how certain parts of these proteins are configured that were difficult to see before, including a part that could help the virus enter human cells. Knowing these structures could help scientists design better HCV vaccines.

Scope of the study

The proteins were analyzed outside the virus, which may not perfectly represent how they look on a real virus. The structure was frozen for study, so it does not show how the proteins might move or change shape. The researchers only looked at proteins from two types of HCV, but there are many more types of liver viruses that may be slightly different. Some parts of a protein were still hard to see clearly, even with this advanced technique.

COMPOSITIONS

This study provides the first detailed insight into how HCV surface proteins are arranged in pairs (homodimers). The structure helps explain how HCV evades antibodies that could fight the infection. The researchers found a “hidden” part of the protein that may be important for the virus to infect cells. This information could be very useful for developing new HCV vaccines. The structure also suggests that the virus may have to change its shape significantly to infect cells, which was previously unknown.

funding

The study was funded by several organizations, including the Novo Nordisk Foundation, the Lundbeck Foundation and the Candys Foundation. The researchers used equipment from the University of Copenhagen and Stockholm, Sweden. The authors have declared that they have no competing interests, meaning that they have no financial or personal relationships that could affect this research.

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