The team screened protein constituents of the ribosome to see which ones might be involved in specialized protein synthesis. Studying the vesicular stomatitis virus, a rhabdovirus in the same family as the rabies virus, they found that its mRNAs depended on rpL40 but only 7 percent of host-cellular mRNAs did. Some of the cellular mRNAs that depend upon rpL40 were stress response genes.
Experiments in yeast and human cells revealed that a class of viruses, which includes rabies and measles, depended on rpL40 for replication.
"This work reveals that the ribosome is not just an automatic molecular machine but instead also acts as a translational regulator," said first author Amy Lee, who is now a post-doctoral researcher at the University of California, Berkeley.
The concept of targeting cellular functions such as protein synthesis for antiviral therapies is being explored by a number of research groups, but there are no drugs based on this.
"We think the principle is bigger than just this single protein," Whelan said. "Viruses have an uncanny way of teaching us new biology all the time."
|Contact: David Cameron|
Harvard Medical School