Marburg virus enters human cells far more efficiently than Ebola

In a new study published in Nature, University of Minnesota researchers found that the Marburg virus, one of the world's deadliest pathogens with an average 73% fatality rate, is unusually efficient at getting inside human cells. They also showed that the virus's entry protein contains structural features that explain this efficiency and point to a strategy for blocking infection.

The researchers designed a tightly controlled system that enables a fair comparison of the entry proteins of Marburg and its relative Ebola. Using this approach, they showed that Marburg's entry protein can drive viral entry into human cells up to 300 times more efficiently than Ebola's. 

The team further found that although the two viruses share the same human receptor, Marburg's entry protein binds this receptor in a distinct orientation and with higher affinity, then changes shape in ways that help the virus enter cells.

Our study establishes a framework for fairly comparing how efficiently different viruses enter cells, which was not possible before. It also links structural features of viral entry proteins to viral infectivity, providing a roadmap for therapeutic interventions. Marburg virus has long been a symbol of highly lethal viruses. Our study helps explain why it is so lethal and identifies a vulnerability that can be exploited by antivirals."

Fang Li, PhD, senior author of the study and professor of pharmacology, University of Minnesota Medical School

The researchers also discovered a tiny antibody, called a nanobody, that can slip past a protective cap on Marburg's entry protein, bind to it and block its attachment to the receptor. In lab tests, this nanobody prevented Marburg virus from entering cells.

Other key contributors include assistant professor Gang Ye, PhD, (Pharmacology), graduate student Fan Bu (Pharmacology), and associate professor Bin Liu, PhD, (The Hormel Institute). This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health [grant U19AI171954] through the Midwest Antiviral Drug Discovery Center.