Researchers at UCLA’s California NanoSystems Institute and other organizations have published a new study on the structure of the bullet-shaped vesicular stomatitis virus, furthering the general understanding of disease treatment and promoting vaccine development.
The virus, which can infect humans and mammals such as cows and horses, is a close relative to viruses such as rabies and influenza.
“We know the structure of the virus and we will be able to understand how the virus assembles itself,” said Peng Ge, the lead author of the study and a visiting graduate student from Baylor College of Medicine. “That will help us … make antivirus medicine,” he added.
The study, published in Science Magazine, provides specific insight on the structure of this unique bullet-shaped virus. Ge described two major applications for vesicular stomatitis virus: vaccine development and medicine for disease treatment. The head of the lab, Z. Hong Zhou, a microbiology, immunology and molecular genetics professor, was out of the country and unavailable for comment.
Ge, who works at the California NanoSystems Institute alongside Zhou, said that scientists mostly knew the structure of the different proteins, but their assembly and interactions in the context of the virus were unclear until now. Now that these scientists have a better understanding of the inner workings of this promising virus, they plan to conduct more research and figure out precisely how the virus gets into cells.
Ming Luo, professor at the University of Alabama at Birmingham, contributed to the findings in the four-year study. He said that incorrect information about the virus has often circulated in the scientific community.
“People didn’t understand how it worked so they made wrong hypotheses and assumptions ““ a lot of experiments were actually wrong,” Luo said. “This new structure will correct all the mistakes people made before. Now we have a solid foundation to build new things and work on new ideas.”
To figure out the structure, the researchers used cryo-electron microscopy to closely examine the virus components. The inner helix of nucleoprotein and ribonucleic acid produces a bullet shape, and the interactions between this helix and the outer layer of protein provide rigidity to the virus. The use of cryo-EM and cryo-electron tomography is “beyond anything anyone’s been able to do before,” said Stan Schein, associate professor of psychology.
Schein, who joined the study out of his interest in molecular structures, is focused on the science behind the work rather than the potential for innovation in medicine.
“Structures are fun, beautiful and interesting in and of itself,” Schein said. “A lot of science is about satisfying your curiosity, not designing some application.”
Yet, the disease-fighting potential of this virus is certainly alluring. While the virus has long been used to experiment with vaccines and disease treatment, Luo said that the newly found structure will impact the way labs and pharmaceutical companies do research in the future.
“We can use this virus as a carrier for vaccines,” Luo said. “We can put flu proteins, HIV proteins, other proteins into this virus to make vaccines.”
Furthermore, by cloaking this bullet-shaped virus with HIV receptors, a “pseudotype” vesicular stomatitis virus is created, which then attracts and binds to HIV-infected cells. The virus selectively kills the infected cells, leaving non-infected cells unharmed, Ge said.
According to in vitro studies, the pseudotype virus has the ability to control HIV infection in cell cultures, he added.
A similar process occurs with cancer cells. Certain “bad” cancers refuse interferon, while “better” cancers are responsive to chemotherapy and can be healed with interferon treatment. Experiments in mice have shown that vesicular stomatitis virus targets interferon-deficient cells, killing “bad” cancer cells, Ge said. Because interferon interferes with the growth of vesicular stomatitis virus, interferon-deficient cancer cells will die while interferon-happy normal cells survive.
The authors expect that their recently published study will lead to further research and more breakthroughs in medicine.
“We’re making progress so we can understand things we didn’t understand before,” Luo said.
“The more we understand, the better we can design new drugs, new medicine or new vaccines,” he added.