NEWS A Swedish variant of the dreaded tick-borne TBE virus causes unusually severe disease in experiments on mice. This is shown in a new thesis at Umeå University. The thesis also shows that for those who are bitten by ticks with TBE infection, their own early immune system plays an important role in preventing the disease from causing damage to the brain.
Ebba Rosendal, PhD student at the Department of Clinical Microbiology, studies an antibody test.
ImageEmil ByströmThis is basic research, but it provides a small piece of the puzzle so that we can eventually outsmart this unpleasant virus
“There is currently no other defence against TBE than to protect oneself against ticks and to make sure to be vaccinated, but hopefully the research will lead to a better understanding of how the virus gets into the brain and, by extension, that we will find curative treatments for the person affected”, says Ebba Rosendal, PhD student at Umeå University.
In her dissertation in virology at Umeå University, Ebba Rosendal has studied how the TBE virus interacts with the body's immune system and what causes the disease symptoms that occur with TBE. Ebba Rosendal and the research group she is part of at the Department of Clinical Microbiology have mapped how the virus infects the brain of mice with or without an early immune response.
They could then see that in cases where the brain's immune system could not be activated, completely different parts of the brain were infected, for example the cells that produce cerebrospinal fluid and the brain's immune cells, microglia. This shows how important the immune system is to those affected by TBE and provides clues about how to help the body fight an infection.
“This is basic research, but it provides a small piece of the puzzle so that we can eventually outsmart this unpleasant virus and perhaps create better treatments for people who have had the misfortune of being infected”, says Ebba Rosendal.
In another part of the thesis, disease-causing factors of the TBE virus were investigated. The researchers discovered that small, naturally occurring changes in the virus's genome can change the surface structure of the virus and thus its ability to cause disease. By comparing several closely related TBE viruses, a Swedish variant of the virus was identified that caused unusually severe disease in mice. This virus strain, so far named 93/783, has two unusual changes in its surface protein. The study showed that these changes affected the virus's ability to infect neurons, cause disease in mice, and how well vaccine-induced antibodies could neutralize the virus.
The discovery may be a clue as to why some people who are infected with TBE from tick bites become sicker than others. The researchers do not yet know how widespread this newly discovered variant is. A problem for the researchers is that once patients seek care for neurological problems caused by the tick-borne TBE virus, the sequelae have progressed so far that it is difficult to find the underlying virus in the patient.
Due to the dangerous nature of the TBE virus, it may only be handled by trained personnel in specialized biosafety laboratories. This makes certain analyzes and methods difficult and time-consuming. As the Umeå researchers are especially interested in the surface proteins of the TBE virus, a new model system has been developed in one of the sub-projects to study these. For this purpose, a relative of the TBE virus that is not dangerous to humans, the Langat virus, has been used, but its surface proteins have been replaced with those of the TBE virus.
The resulting virus looks like the TBE virus but behaves like the Langat virus in cell culture and in mice. This makes it a very useful tool for studying various aspects linked to the surface structure of the virus, such as the antibody response after TBE vaccination.
Tick-borne encephalitis, TBE, is a neurological disease caused by the TBE virus. Each year, 300-500 cases of TBE are reported in Sweden alone. The consequences of an infection can be very serious and lead to long-term functional impairments.
Ebba Rosendal grew up on a horse farm outside Fagersta in Västmanland. Before she came to Umeå to research viruses, she studied engineering in Lund.
Ebba Rosendal, Department of Clinical Microbiology at Umeå University, defended on Friday 26 May her thesis Host-pathogen interactions during tick-borne flavivirus infection: pathogenesis, tropism and tools. Opponent Sonja Best, The National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA. Main supervisor Anna Överby Wernstedt.
