Scientists from The Scripps Research Institute (TSRI) have been awarded $6.6 million from the National Institutes of Health (NIH) to lead an investigation of Lassa fever virus, the most prevalent virus-induced hemorrhagic fever disease in Africa. The study aims to understand how Lassa fever virus causes disease and why some patients die, while others survive the inflection.

This transmission electron micrograph (TEM) depicted numbers of Lassa virus virions adjacent to some cell debris. Image/C. S. Goldsmith
This transmission electron micrograph (TEM) depicted numbers of Lassa virus virions adjacent to some cell debris. Image/C. S. Goldsmith

“The ultimate goal is for researchers to understand the basic mechanism of how Lassa fever virus causes disease and develop new treatments to be used by clinicians to fight this malady,” said TSRI Professor Michael Oldstone, principal investigator of the new grant.

Lassa fever is spread by rodents and is common in West Africa, where it kills an estimated 30,000 to 40,000 people every year—approximately 10 to 15 percent of those infected. The virus can pass from human to human, causing devastating outbreaks of a hemorrhagic disease similar to Ebola virus.

This five-year study focuses on how the immune system fights off Lassa fever virus and how the virus can confound the immune system. To date, little is known about how the body’s innate immune response (interferons, cytokine proteins, inflammatory cells) and adaptive immune response (T and B cells, antibodies) react to the hemorrhagic virus infections.

One TSRI investigator, Brian Sullivan, will work both in La Jolla and in Sierra Leone on the project. A hospital, specialized hemorrhagic fever ward and containment laboratory have been established in Sierra Leone with doctors and nurses there to treat patients and collect blood and tissue. Samples are handled at the containment laboratory. Other samples will go to team members in the United States, including groups led by Oldstone, Sullivan and Juan Carlos de la Torre at TSRI and by Pardis Sabeti at Harvard University and Robert Garry at Tulane University.

“Not a lot of research has been done on neglected tropical fevers like Lassa, which cause profound public health and economic problems,” said Sullivan. “I think we’ll get a lot of answers to important questions that haven’t been asked before.”

Studies will include analysis of cells and chemicals of the innate and adaptive immune response, mapping the genetics of patients who survive and those who do not. In addition, the team will follow up on previous studies suggesting that there is an unusually high mutation rate in individuals living in Lassa fever-endemic areas and that these mutations may play an important role in the rate of survival of patients.

Related: The World’s Deadliest Viruses