Antibodies stop tissue damage and reduce virus levels in mice with deadly Crimean-Congo hemorrhagic fever

Researchers studying a deadly virus discovered a key protein behind its lethality and successfully used antibodies to stop that protein from causing dangerous fluid leakage in mice.

The results, published in Science Translational Medicine on Feb. 19, could pave the way to the first treatment or vaccine for Crimean-Congo hemorrhagic fever virus (CCHFV).

Primary funding for the study came from the National Institutes of Health.

The researchers, led by virologist Eva Harris, Ph.D., of the University of California, Berkeley, first examined mice infected with CCHFV and determined that a protein called GP38, released by cells infected with the virus, disrupts the thin layer of tissue that lines blood vessels. This causes vascular leakage, when fluids leak out of blood vessels and soak into surrounding tissues, which helps the virus spread throughout the body.

Once GP38’s role in the disease was confirmed, the team tested a suite of antibodies that bind to the protein to see whether any stopped its effects. 

Treating mice with anti-GP38 antibodies reduced the amount of vascular leakage and levels of GP38 in the blood and prevented CCHFV from spreading into new tissues, the team found.

“This study provides evidence that GP38 is a CCHFV virulence factor or viral toxin with a direct role in viral pathogenesis,” the authors wrote in their study. “Our findings emphasize the importance of including GP38 in CCHFV vaccine design and provide a starting point for the rational design of GP38-targeting anti-CCHF therapeutics.”

There are currently no treatments for CCHFV beyond targeting symptoms, which include fever, muscle aches and abdominal pain. The disease is often fatal, with a mortality rate that can reach as high as 40%, according to the new study.

CCHFV is primarily spread by ticks in the genus Hyalomma, but it can also spread between humans through close contact with the body fluids of an infected individual. The disease occurs primarily in Africa, Asia, the Middle East and the Balkans, the areas where the tick that spreads it lives, according to the World Health Organization.