Researchers at Duke-NUS Medical School along with scientists from the University of North Carolina, have discovered the mechanism by which C10, a human antibody previously identified to react with the Dengue virus ( one of the viruses I spoke about in my previous blog), prevents Zika infection at a cellular level. The researchers have determined how C10 is able to prevent infection. To infect a cell, virus particles usually undergo two main steps, docking and fusion. The way Zika works is first by docking, docking then initiates the cell to take the virus to a separate compartment within the cell body. Proteins within the virus coat undergo structural changes to fuse with the membrane of the endosome, which then release the virus genome into the cell, and complete the fusion step of infection. Using cryoelectron microscopy they were able to visualize C10 interacting with Zika at different pHs that they might come across during the infection process. This means that C10 binds to the main protein that makes up the Zika virus coat, regardless of pH, and locks these proteins into place which does NOT allow the changes to be made to the structure that is needed in order for fusion to take place. Without fusion of the virus to the endosome, viral DNA can not enter the cell and the infection will stop. The researchers are hoping that this will open up doors for more research to take place in the development into Zika therapy. They also believe that disrupting fusion with C10 could be more effective in preventing Zika as opposed to working towards disrupting the docking step. Why do they believe that disrupting fusion would be better than disrupting blocking? Because the fusion step is critical for Zika to infect the cell, while the virus can develop other ways to overcome the disruption to the docking step. I sincerely hope that all this research is going to hopefully one day develop a way to eradicate this disease.
Journal Reference:
- Shuijun Zhang, Victor A. Kostyuchenko, Thiam-Seng Ng, Xin-Ni Lim, Justin S. G. Ooi, Sebastian Lambert, Ter Yong Tan, Douglas G. Widman, Jian Shi, Ralph S. Baric, Shee-Mei Lok. Neutralization mechanism of a highly potent antibody against Zika virus. Nature Communications, 2016; 7: 13679 DOI: 10.1038/NCOMMS13679
