Surprising discovery about the inner workings of vesicular stomatitis virus

Biochemists at Wake Forest University School of Medicine have made a surprising discovery about the inner workings of a powerful virus - a discovery that they hope could one day lead to better vaccines or anti-virus medications.

Reporting in the April issue of the Journal of Virology, the researchers have identified a protein that plays an important role in the ability of the vesicular stomatitis virus (VSV) to invade healthy cells and reproduce itself. The finding could play a role in vaccine development and also help scientists develop anti-viral agents to stop similar viruses in their tracks.

Although VSV infects animals, it is not a human pathogen. Nevertheless, scientists study it because of its similarity to viruses such as Ebola and Marburg hemorrhagic fever viruses, as well as rabies virus. "VSV is a good model of a variety of other viruses," said John Connor, Ph.D., a research assistant professor of biochemistry. "Our research has given us a better understanding of how viruses like these are able to do the nasty things they do."

The scientists set out to study the role of a protein known as "matrix," which is produced by VSV. They suspected matrix was important in how VSV is assembled, but unexpectedly discovered the matrix protein is critical in how the virus reproduces and spreads. When they altered the matrix protein, they weakened the virus' ability to reproduce. The finding has several important implications, Connor said.

Normally, VSV is extremely powerful, with the ability to shut down a cell's system for making proteins. VSV then takes over the cell's protein-making machinery and makes its own proteins so it can replicate and spread. The scientists were able to weaken this power by altering the matrix protein, so that VSV cannot make as much protein and does not reproduce as well.

Weakened viruses such as this are often used to make vaccines because they are less likely to be harmful. Currently, another weakened form of VSV is being used for a HIV vaccine that is being tested in humans. To make the vaccine, scientists started with the weakened VSV virus and added a protein from the HIV virus so that VSV "expresses" or makes a fragment of the HIV virus. In theory, when people are inoculated with the vaccine, they will develop antibodies to the HIV protein, and if they are exposed to the actual HIV virus, their bodies will neutralize it and kill it before it infects them.

In all, several weakened forms of VSV have been developed and at least two are currently being tested in HIV vaccines. If they don't prove effective, vaccine developers can turn to one of the others, including the mutant VSV virus developed by Connor and colleagues.

"Right now, there's no way of knowing which way of weakening the virus will make the best vaccine," Connor said.

In addition to its potential for vaccine development, the new finding about VSV also provides basic information about how the virus shuts downs a cell's protein making-abilities and dominates the process.

"We always knew this happened, but the process was like a black box," said Connor. "Now, we know that the matrix protein is involved and is incredibly important in virus reproduction. This pushes forward our knowledge of how this virus is so effective at replicating."

Could the finding about matrix be used to weaken other types of viruses? The scientists aren't sure, yet. "It's a strong possibility that every virus will have an Achilles' heel like this, where they need the function of a viral protein to make lots of virus," said Connor.