Study offers insights into potential for vaccine for hepatitis C
Researchers identify protein complex that allows infection
Researchers have uncovered the structure of the protein complex that allows the hepatitis C virus (HCV) to infect human cells, allowing them to reproduce and study it in the lab. This new information could lay the foundation for the design of a preventive vaccine for hepatitis C.
“We are the first ever to identify the protein complex at the surface of the hepatitis C virus that enables it to bind to our cells,” Jannick Prentø, PhD, the study’s senior author and an associate professor at the University of Copenhagen, said in a university news story.
The findings were described in the study, “The hepatitis C virus envelope protein complex is a dimer of heterodimers,” published in Nature.
“This knowledge of the structure of the protein complex will enable us to design vaccine candidates that can prevent the virus from infecting the cells,” said University of Copenhagen Assistant Professor Elias Augestad, PhD, who worked on the project as a postdoctoral researcher and was the study’s first author.
Vaccines and proteins
HCV is a common cause of hepatitis, or inflammation of the liver, affecting more than 50 million people worldwide. While about a quarter of people will naturally clear the virus in the first months of infection, the rest go on to develop a chronic form of hepatitis C that can lead to serious liver problems.
The virus is usually spread via exposure to blood from an infected person, such as sharing contaminated needles. Despite worldwide efforts to eliminate viral hepatitis, deaths from these liver infections continue to rise.
While there are vaccines available to prevent other viral causes of hepatitis, including hepatitis A and B, there is no such vaccine to ward off hepatitis C.
Viruses, including hepatitis viruses, have protein complexes on their surface that are crucial for their ability to bind to human cells. Without them, the viruses are not able to successfully infect cells.
Many vaccines are therefore designed to help the immune system produce antibodies that will recognize and attack these critical protein complexes, rendering the virus unable to cause an infection.
One reason it has been difficult for scientists to develop a hepatitis C vaccine is that they hadn’t previously understood enough about the protein complexes that HCV uses to bind to human cells.
Visualizing structure
It was known that two HCV envelope proteins called E1 and E2 bind together, forming a structure called a heterodimer, which would be the optimal target for an HCV vaccine. But the exact structure of that complex, and how it may help HCV bind to human cells, remained unclear.
“The structure of these proteins on the surface of the hepatitis C virus makes them extremely vulnerable,” Prentø said. “Researchers did not know what they were dealing with, and therefore, whenever someone tried to reproduce these protein structures in the lab they would fall apart before they could get a chance to study them.”
Using an advanced microscopy technique, the scientists were able to visualize the structure of the E1/E2 heterodimers from HCV viral strains grown in the lab.
“We managed to describe their structure, and this has enabled us to reproduce these protein complexes outside the cell and study them closely,” said Pontus Gourdon, PhD, one of the study’s authors and an associate professor at the University of Copenhagen.
The team gathered important information about the mechanisms by which the protein complex helps the HCV fuse to human cells. They also learned more about the weak points in this complex, and where neutralizing antibodies, such as those produced from a vaccine, can bind to.
The researchers will now be able to use the information to conceptualize a vaccine for hepatitis C prevention.
“This complex offers several key insights into the biology of HCV … and provides a framework for designing a new type of HCV vaccine,” the researchers wrote.
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