(WUTR / WFXV / WPNY) – You may have learned in science class that your body makes antibodies to fight viruses that make you sick. The way they work is by hooking onto a virus and preventing 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 antibodies turn off viruses. An international team of researchers led by Penn State has found that antibodies can also distort viruses. “Our research shows for the first time that antibodies can also physically distort viruses so that they are unable to attach properly 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 the human monoclonal antibody (HMAb) C10 and two pathogenic viruses: Zika and dengue. The HMAb C10 antibodies they were using had previously been isolated from patients infected with the dengue virus and had also been shown to neutralize the 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 researchers to see viruses. The second technique was hydrogen / deuterium exchange mass spectrometry (HDXMS), which allowed researchers to understand how viruses move. This involves taking molecules of interest (such as Zika and the dengue virus, as well as HMAb C10 antibodies) and submerging them in heavy water. Heavy water, Anand explained, saw its hydrogen atoms replaced by deuterium, the heavier isotopic cousin of hydrogen.
âWhen you submerge a virus in heavy water, the hydrogen atoms on the surface of the virus exchange with deuterium,â he said. âWe can then use mass spectrometry to measure the heaviness of the virus as a function of this deuterium exchange. In doing so, we observed that the dengue virus, but not the Zika virus, got heavier with deuterium as more antibodies were added to the solution. This suggests that for the dengue virus, the antibodies distort the virus and allow more deuterium to enter. It is as if the virus is crushed and a larger area is exposed where hydrogen can be exchanged for deuterium.
In contrast, the Zika virus did not become heavier when placed in heavy water, suggesting that its surface, although fully occupied by antibodies, is not deformed by antibodies.
He noted that the more antibodies they added, the more deformed the dengue virus particles, suggesting that stoichiometry (the relationship between the amounts of reagents and products before, during, and after a chemical reaction) is important. . “It is not enough to have antibodies present,” he said. “The amount of antibody you add determines the extent of neutralization.”
What does this mean for the future? Well, one avenue that this research can open is that of therapeutics. âHMAb C10 antibodies are specific to dengue and Zika viruses and are able to neutralize Zika and dengue viruses in two different ways … By creating therapy with antibodies that can both block and deform viruses, we can possibly achieve greater neutralization. Said Anand.
He added: “You don’t want to wait for a virus to reach its target tissue, so if you can introduce a therapeutic cocktail such as a nasal spray where the virus first enters the body, you can prevent it even. By doing this you may even be able to use fewer antibodies since our research shows that it takes less antibody to neutralize a virus by the distortion method. money.
Overall, Anand stressed that the importance of the study is that it reveals a whole new strategy that certain antibodies use to deactivate certain viruses.
âPreviously all we knew about antibodies was that they bind to and neutralize viruses,â he said. âNow we know that antibodies can neutralize viruses in at least two different ways, and maybe even more. This research opens the door to a whole new avenue of exploration.