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How the Crimean-Congo hemorrhagic fever virus enters our cells

Researchers at Karolinska Institutet, in collaboration with JLP Health and others, have identified how the tick-borne Crimean-Congo hemorrhagic fever virus enters our cells. The results are published in nature microbiology and are an important step in the development of drugs against this deadly disease.

The Crimean-Congo hemorrhagic fever virus (FCHF virus) is transmitted through tick bites and can cause hemorrhagic fever. The disease is serious and has a mortality rate of up to 40 percent depending on the health status of the infected person. Common symptoms include fever, muscle pain, abdominal pain, joint pain, vomiting, and bleeding that can cause organ failure.

The disease has spread to Europe.

The virus is present in about 40 countries, including Central Asia, the Middle East and parts of Africa. In recent years, the disease has spread to new geographic areas as a result of climate change, including Spain and France. Tick ​​species that can transmit the disease have also been observed in Germany and Sweden. There are currently no effective treatments for the disease.

In a new study, researchers from Sweden’s Karolinska Institute and others have discovered that the virus enters our cells through a protein on the cell surface, the so-called LDL receptors that regulate blood cholesterol levels.

To identify the protein, the researchers used human mini organs grown in test tubes and an advanced stem cell library from JLP Health. The same platform has previously been used to identify how the Ebola virus enters cells.

The results were also confirmed in tests on mice, which showed that mice lacking the LDL receptor did not get as sick as the others.

Researchers want to trick the virus

The discovery is an important step toward developing drugs for Crimean-Congo hemorrhagic fever, according to Ali Mirazimi, associate professor at the Department of Laboratory Medicine at Karolinska Institutet and one of the researchers behind the study.

“Once we know which receptor the virus uses, we can produce it in test tubes and administer it as a drug,” he says. “Then we can trick the virus into binding to those receptors instead of cells and thus stop the spread of the virus in our bodies.”

This knowledge is essential for the disease to become more common and spread to new areas. It normally takes many years to develop a drug, but the COVID-19 pandemic and the development of the SARS-CoV-2 vaccine showed that it can be done much faster if everyone decides it is a priority.

Ticks are transmitted by migratory birds.

“This is an important step in our preparation for the disease,” says Ali Mirazimi. “Crimean-Congo hemorrhagic fever is a disease we would prefer not to have. Ticks are transmitted by migratory birds and have already been found in Sweden. If the disease starts to appear in more places, we may already have a medicine that we can take in clinical trials.”

The research was carried out in collaboration with the Medical University of Vienna, Austria, the Helmholtz Center for Infection Research, Germany, the National Institutes of Health, USA and the company JLP Health. It was mainly funded by the Swedish Research Council and the EU. No conflicts of interest have been reported.