Scientists at the Austrian IST discovered the principle of assembly of the HIV-associated Lloyd's sarcoma virus, which pushed viral research forward. Viruses are the perfect molecular machine. Their only goal is to insert their genetic material into healthy cells for reproduction. Because of their lethal precision, they can therefore cause disease, kill millions of people, and put the world in a state of tension.
Rau's sarcomavirus, although less discussed at the moment, and HIV, which has led to the global AIDS epidemic, has killed 690,000 people from infection with the virus in 2019 alone, despite advances in response in recent years.
Martin Ober, a postdoc in the Shure group at the Austrian University of Science and Technology, said that together with his colleagues he was studying a virus that belongs to the same family as HIV — ruth sarcoma virus, a virus that causes cancer in poultry. With its help, he now has a new understanding of the important role that a small molecule plays in the assembly of these types of viruses.
In their study, published in the journal Nature Communications, the team, along with collaborators at Cornell University and the University of Missouri, focused on the later stages of retroviral replication. Lead author Martin Obr explains: "It's a long road from an infected cell to a mature viral particle capable of infecting another cell. "
Proteins with viral shells that contain genetic information have a much more flexible shape than previously thought. Small IP6 molecules (0:38) stabilize the hexamers (gray) and pentamers (orange) of the protein.
By further developing cryogenic electron tomography, postdoc Martin Obr was able to gain new insights into how viruses protect their genetic material.
A new particle sprouts from the cell in an immature, non-infectious state. It then forms a protective shell around its genetic information, the so-called cap," and becomes contagious. This protective shell consists of a protein that is organized into hexamers and some pentamers. The team found that a small molecule called IP6 plays an important role in stabilizing the protein shell within the Ross sarcoma virus.
"If the protective shell is unstable, the genetic information of the virus may be released prematurely and will be destroyed, but if it is too stable, the genome simply cannot exit and, as a result, becomes useless," said Assistant Professor Florian Schur.
In a previous study, he and his colleagues were able to demonstrate that IP6 is important during THE HIV assembly process. Now, the team has demonstrated its importance in other retroviruses, showing how important this small molecule is in the life cycle of the virus.
"When you build a car, you have all these big metal parts like the hood, the roof and the doors – screws connect everything. In our case, the large parts are cap-like proteins, while the IP6 molecules are screws," Obr said.
Cryogenic Electron Tomography — a technique that allows scientists to observe extremely small samples in their natural state — allows the team to see how varied the shapes formed from cap-like proteins are.
Further developing technology to understand these highly optimized pathogens remains a challenging and attractive task for scientists.