An atomic-level investigation of how Eastern equine encephalitis virus binds to a key receptor and gets inside of cells also has enabled the discovery of a decoy molecule that protects against the potentially deadly brain infection, in mice.
The study, from researchers at Washington University School of Medicine in St. Louis, is published Jan. 3 in the journal Cell. By advancing understanding of the complex molecular interactions between viral proteins and their receptors on animal cells, the findings lay a foundation for treatments and vaccines for viral infections.
“Understanding how viruses engage with the cells they infect is a critical part of preventing and treating viral disease,” said co-senior author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor at Washington University. “Once you understand that, you have the foundation for developing vaccines and drugs to block it. In this study, it took us a long time to sort out the complexity associated with the particular receptor-virus interaction, but once we acquired this knowledge, we were able to design a decoy molecule that turned out to be very effective at neutralizing the virus and protecting mice from disease.”
Though infections of Eastern equine encephalitis virus in people are rare — with only a few cases reported worldwide each year — about one-third of those with the infection die, and many survivors suffer lasting neurological problems. Further, scientists predict that as the planet warms and climate change lengthens mosquito populations’ seasons and geographical reach, risk of infection will grow. At present, there are no approved vaccines against the virus or specific medications to treat it.
As a first step to finding ways to treat or prevent the deadly virus, Diamond and co-senior author Daved H. Fremont, PhD, a professor of pathology and immunology, set about investigating how the virus attaches to one of its key receptors — a molecule called VLDLR, or very-low density lipoprotein receptor. The molecule is found on the surface of cells in the brain and other parts of the body. Co-first author Lucas Adams, an MD/PhD student in the Fremont and Diamond laboratories, used cryo-electron microscopy to reconstruct the virus binding to the receptor in atomic-level detail.