Antibodies help the body fight off viruses by attaching themselves to the surface of viral particles, essentially disabling the pathogens by blocking them from entering cells. However, new research has revealed another ability in the antibody toolkit that could lead to new strategies for combating viruses such as dengue. A study conducted by Penn State researchers found that the human monoclonal antibody (HMAb) C10 can induce distortions on the surface of the dengue virus, further impeding its ability to infect cells.
The research team conducted studies using cryogenic electron microscopy (cryo-EM) and hydrogen/deuterium exchange mass spectrometry (HDXMS) to better understand how HMAb C10 interacts with dengue and Zika molecules. For both methods, increasing concentrations of antibodies were used to analyze the stoichiometry of the reactions. The researchers found that at higher concentrations of antibodies, the dengue molecules became distorted, evidenced by both the cryo-EM snapshots and level of deuterium exchange. The Zika virus, however, did not show this same distortion, suggesting that differences in the surface structures played a part in the reactions.
Specifically, the researchers found that when dengue molecules were fully bound with antibodies at their 5-fold and 3-fold vertices, the remaining antibodies would begin “burrowing into the virus,” leading it to distort and cease to function normally, according to corresponding author Ganesh Anand. The Zika virus, which has fewer “moving parts,” is more easily disabled through conventional antibody binding and does not trigger this “burrowing” behavior, Anand explained.
The researchers reported that at high enough antibody concentrations, up to 60% of the dengue virus’ surfaces became distorted, and incubating antibody-body bound dengue viruses with BHK-12 cells resulted in 50-70% fewer cells being infected. This research was published in the journal Cell.
“Previously, all we knew about antibodies was that they bind and neutralize viruses,” Anand said. “Now we know that antibodies can neutralize viruses in at least two different ways, and perhaps even more. This research opens the door to a whole new avenue of exploration.”
While this study was focused on HMAb C10 antibodies and their dengue and Zika virus targets, the researchers said these new insights could lead to further discoveries that may enable more effective treatments to neutralize and distort other viruses.
Photo: The same type of antibody can neutralize Zika and dengue viruses in two different ways — one where it binds to the virus and deactivates it (left), which is the traditional way we think about antibody activity, and the other where it burrows in and distorts the virus (right). Credit: Ganesh Anand, Penn State