(WUTR/WFXV/WPNY) – You might have learned in science class that your body creates antibodies to fight off viruses that make you sick. The way they work is by latching onto a virus and blocking it from infecting host cells. This is a widely understood concept of how antibodies neutralize viruses. New research however has revealed that this barrier method isn’t the only way that antibodies disable viruses. An international team of researchers led by Penn State has discovered that antibodies can also distort viruses. “Our research reveals for the first time that antibodies may also physically distort viruses, so they are unable to properly attach to and infect host cells.” said Ganesh Anand, associate professor of chemistry at Penn State.
In their study, Anand and his colleagues investigated the interactions between human monoclonal antibody (HMAb) C10 and two disease-causing viruses: Zika and dengue. The HMAb C10 antibodies they used had previously been isolated from patients infected with dengue virus and also had been shown to neutralize Zika virus. To see and understand the interactions between these antibodies and viruses, the researchers used a combination of techniques. One technique used was cryogenic electron microscopy (cryo-EM), which allowed the researchers to see the viruses. The second technique was hydrogen/deuterium exchange mass spectrometry (HDXMS), which allowed the researchers to understand how the viruses move. It involves taking molecules of interest (like Zika and dengue virus, along with HMAb C10 antibodies) and submerging them in heavy water. Heavy water, Anand explained, has had its hydrogen atoms replaced with deuterium, hydrogen’s heavier isotopic cousin.
“When you submerge a virus in heavy water, the hydrogen atoms on the surface of the virus exchange with deuterium,” he said. “You can then use mass spectrometry to measure the heaviness of the virus as a function of this deuterium exchange. By doing this, we observed that dengue virus, but not Zika virus, became heavier with deuterium as more antibodies were added to the solution. This suggests that for dengue virus, the antibodies are distorting the virus and allowing more deuterium to get in. It’s as if the virus is getting squished and more surface area becomes exposed where hydrogen can be exchanged for deuterium.”
In contrast, Zika virus did not become heavier when placed in heavy water, suggesting that its surface, while fully occupied by antibodies, is not distorted by the antibodies.
He noted that the more antibodies they added, the more distorted the dengue virus particles became, suggesting that stoichiometry (the relationship between the quantities of the reactants and the products before, during, and after a chemical reaction) matters. “It’s not enough to just have antibodies present,” he said. “How much antibody you add determines the extent of neutralization.”
What does this mean for the future? Well, one avenue this research can open up is with therapeutics. “HMAb C10 antibodies are specific to dengue and Zika viruses, and happen to be capable of neutralizing Zika and dengue viruses in two different ways… But you could potentially design therapeutics with the same capabilities for treating other diseases, such as COVID-19. By creating a therapeutic with antibodies that can both block and distort viruses, we can possibly achieve greater neutralization.” Anand said.
He added, “You don’t want to wait for a virus to reach its target tissue, so if you can introduce such a therapeutic cocktail as a nasal spray where the virus first enters the body, you can prevent it from even entering the system. By doing this, you may even be able to use less antibody since our research shows that it takes less antibody to neutralize a virus through the distortion method. You can get better bang for the buck.”
Overall, Anand stressed that the importance of the study is that it reveals an entirely new strategy that some antibodies use to disable some viruses.
“Previously, all we knew about antibodies was that they bind and neutralize viruses,” he 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.”