Dr. Scott Biering, a California finalist for the Michelson Philanthropies & Science Prize, wrote about a conserved flavivirus protein that holds potential as a target for versatile vaccines and therapies.
By Justin Chapman
Understanding the Role of Viral Proteins
Dr. Scott Biering, a finalist for the prize, is a molecular virologist and immunologist at UC Berkeley School of Public Health’s Division of Infectious Diseases & Vaccinology. His research investigates the role of viral proteins like flavivirus nonstructural protein 1 (NS1) and SARS-CoV-2 spike in inducing viral pathogenesis and promoting viral dissemination. For the Michelson Prize, he wrote about a conserved flavivirus protein that holds potential as a target for versatile vaccines and therapies.
When he joined Dr. Eva Harris’ lab at Berkeley, they had just discovered that NS1, which circulates in the blood of flavivirus-infected patients, contributes to endothelial dysfunction. This protein was always used as a diagnostic for dengue fever because early dengue infection looks like a lot of infections from other pathogens in subtropical-tropical areas. The beginnings of these infections look similar, so how would doctors know whether to treat patients for malaria, flavivirus infection, or bacterial infection? NS1 was originally used to differentiate that.
NS1 directly interacts with endothelial cells and immune cells and that is a direct trigger of vascular leak. When Dr. Biering joined the lab, he wanted to understand how this occurs and also how doctors can protect patients against this specific pathogenesis.
“What our study did that pushed our knowledge of NS1 to the next level is, it used structural biology to teach us exactly how NS1 causes endothelial dysfunction,” he said. “We could show which specific domains of NS1 contribute to pathogenesis by using this dengue virus protective anti-NS1 antibody that we’ve been using in the laboratory for other purposes for a long time. But because the antibody bound to a very flavivirus conserved area, it led to the natural question: could you protect against multiple flaviviruses with this? In vitro, we demonstrated that this antibody could block endothelial dysfunction against three major flavivirus NS1 proteins: dengue, Zika, and West Nile. Some of our research now is going on to expand this concept to see how we can achieve better protection and the development of more therapeutics focused on the NS1-binding epitope of our antibody.”
Emerging Viruses and Lessons Learned
Dr. Biering said he is also applying lessons learned from his NS1 research toward multiple emerging viruses.
“Many serious viral infections become systemic, and the way viruses become systemic or disseminate throughout the body are not well understood,” he said. “We find that NS1 proteins from diverse flaviviruses cause a tissue-specific pattern of endothelial dysfunction that mirrors the disease manifestations of their respective viral infections, so we are very interested to determine if/how viral proteins like flavivirus NS1 facilitate viral dissemination of a given virus across endothelial barriers and into specific tissues.” “This would explain why our anti-NS1 antibody is so protective against flavivirus infection, because it stops the virus from disseminating throughout the body.”
He added that from a public health perspective, he wants his work to have a translational element that will alleviate infectious diseases, because flaviviruses aren’t going anywhere.
“We have to be ready for the next viruses that come. We have to understand general themes that all viruses use to cause disease and be ready for that before we even see it.” —Dr. Scott Biering
“Problems are only going to get worse as the human population grows, moves into new areas, lives in closer proximity with livestock, and with climate change and whatnot,” he said. “We have to be ready for the next viruses that come. We have to understand general themes that all viruses use to cause disease and be ready for that before we even see it.”
Learn more about the Michelson Philanthropies & Science Prize for Immunology here.
Watch the full video about Dr. Biering’s research: