Study finds genetic factors for severe Lassa fever

NEW YORK: An international team of scientists has identified genetic factors that cause severe Lassa fever -- an infection that is caused by the Lassa virus.

Lassa fever is endemic in West Africa, and can be deadly in some people while only mild in others.

The virus causes fever, sore throat, coughing, and vomiting, but can quickly progress to organ failure in some people.

The study published in the journal Nature Microbiology found two key human genetic factors that could help explain why some people develop severe Lassa fever, and a set of LARGE1 variants linked to a reduced chance of getting Lassa fever.

The findings could lay the foundation for better treatments for Lassa fever and other similar diseases, like Ebola, said the researchers Harvard University in the US and Redeemer's University in Nigeria.

For the study, the team compared the genomes of about 500 people who had Lassa fever and nearly 2,000 who had not.

In the Nigerian cohort, the team found that people with a set of variants in the LARGE1 gene -- which modifies a cell receptor that binds to certain viruses -- were less likely to get Lassa fever.

The researchers also found genomic regions associated with Lassa fatality: in the LIF1 gene, which encodes an immune-signaling molecule, and, in the Nigerian cohort, the GRM7 gene, which is involved in the central nervous system.

The team then used a large-scale screen called a massively parallel reporter assay to home in on which variants within these genomic regions might be functional and could be targets of new treatments.

The researchers noted that to improve detection and treatment of Lassa fever, more diagnostic centers and diagnostics that work in the field are needed, along with better health infrastructure to connect remote locations with major hospitals.

"This really highlights the need for continued investment in understanding African population genetics," said Siddharth Raju, a graduate student at the Harvard.

"Even with a relatively limited sample set, we’ve increased our understanding of some African populations, specifically in immune-related genes -- and that shows how much more there is to do going forward," he added.

The team said the work also shows that, as thoughtful collaborations between countries, genome-wide association studies of BSL-4 viruses are possible.

The researchers have already begun conducting a similar study of Ebola in Sierra Leone and Liberia, and other scientists are calling for increased pathogen surveillance and scientific training in Africa.