CDC / Charles Humphrey
Scientists have discovered the structure of a key piece of protein that deadly arenaviruses use to enter and infect human cells. The research could help in developing a vaccine for Lassa fever and other related diseases, according to a decade-long study.
Lassa fever is one of three top vaccine priorities for the Coalition for Epidemic Preparedness. The viral hemorrhagic fever is endemic in West Africa, where it infects 100,000 to 300,000 people a year and can be fatal.
"The ten years of protein engineering to get there now provide the direct blueprints needed to make the right shape of Lassa molecule and display it on vaccines, and to begin to make the right shape of molecule for other arenaviruses," says Erica Ollmann Saphire, one of the study's authors from the The Scripps Research Institute.
Study details: The structure of a key protein on the surface of the virus, which is what antibodies from a potential vaccine could target, is not stable enough to study with x-ray crystallography, a standard technique for determining the atomic and molecular structure. Over ten years, the researchers worked to engineer different parts of the protein that they then assembled into a version that didn't fall apart. They then used x-ray cystallography to reveal the structure.
The structure: The protein consists of three sets of two-part subunits that come together like a tripod to infect the host cell. When the scientists tested antibodies from patients who had Lassa fever and recovered, they found that 90% of those antibodies that could neutralize the virus targeted the molecule at the tripod junction and basically locked the subunits together, preventing the virus from entering a host cell.
Lassa fever: The majority of infections occur in West Africa, where the primary agent is the urine or feces of an infected rat sometimes transmitted through contaminated food or air. The overall fatality rate for Lassa Fever is between 1 and 10 percent, but the rate among patients hospitalized with severe disease is between 50 and 70 percent. Notably, the disease is 90 percent lethal for women in the third trimester of pregnancy.