Scientists Discover "Bald Spots" in the Envelope of the Tick-Borne Encephalitis Virus

Using modern methods, researchers led by experts from Masaryk University have surprisingly discovered that the tick-borne encephalitis virus is not as perfectly organized as previously thought. There are areas on its surface where part of the protein coat is missing and the viral membrane is exposed. It is precisely this incompleteness of the particles that showed that the rearrangement of surface proteins does not begin simultaneously across the entire virus, but at a single point from which it gradually spreads across its surface. The discovery also suggests that the same principles apply to the entire group of flaviviruses, which also includes the dengue, Zika, and yellow fever viruses.

A new discovery helps explain why some antibodies can effectively neutralize the virus, even though their target sites were previously thought to be inaccessible.

Using cryo-electron microscopy and electron tomography, the researchers observed thousands of tick-borne encephalitis virus particles—which belong to the flavivirus family—and found that many of them deviate significantly from the ideal model. “In textbooks, flaviviruses are usually depicted as perfectly symmetrical particles. However, our data show that many immature and mature viral particles contain exposed areas where part of the protein envelope is missing. It is precisely these imperfections that have helped us better understand how viruses assemble and mature,” says Tibor Füzik of CEITEC at Masaryk University, the study’s principal investigator.

The arrangement of surface proteins at the edges of these exposed regions shows that the viral envelope of an immature particle is assembled step by step from individual proteins. The new data also suggest that the rearrangement into a mature structure occurs gradually around a randomly formed center and expands as individual building blocks are added to its edges.

Under normal circumstances, some parts of the virus’s surface proteins are hidden because they fit tightly together, making them difficult for antibodies to access. However, if a part of the virus is not completely covered by proteins, the normally hidden parts of the proteins are exposed. Consequently, antibodies—molecules that the immune system uses to recognize and neutralize viruses—can bind to these sites. This new discovery thus helps explain why some antibodies can effectively neutralize the virus, even though their target sites were previously considered inaccessible.

According to the study’s authors, this principle may not be limited to the tick-borne encephalitis virus. “We believe that similar rules of assembly and maturation may also apply to other flaviviruses, such as dengue, Zika, or yellow fever viruses, which cause millions of infections worldwide every year,” adds Pavel Plevka, head of the research group at CEITEC MU.

Thanks to these new findings—on how flaviviruses assemble and mature into their infectious form—scientists can better understand how the immune system recognizes viral particles and contribute to the future development of antiviral drugs or vaccines.

Research teams from the University of Helsinki and the Faculty of Science at Masaryk University participated in the study. The study was published in the journal Science Advances.