When viruses set up camp inside the cells of animals and plants, they need to replicate before being detected and destroyed by the host cell. Now researchers have uncovered a trick that gives viruses an edge in this race against time. Surprisingly, the findings suggest that groups of viruses long thought to be distinct share a common replication mechanism.
Molecular virologist Paul Ahlquist and co-workers at the University of Wisconsin, Madison, investigated virus replication in a research workhorse known as brome mosaic virus (BMV). BMV is one of the so-called positive-stranded RNA viruses, a class that includes the perpetrators of well-known diseases: hepatitis C, West Nile disease, foot-and-mouth disease, polio, rubella, and the common cold. In a 1998 paper, Ahlquist's team found that a protein known as BMV 1a dramatically prolonged survival of the viral RNA in yeast cells. But they didn't know how the protein did this.
To investigate, Ahlquist and colleagues expressed the virus's replication genes in yeast cells. They found that BMV 1a cooperates with two other viral elements--an enzyme known as 2a polymerase and an RNA sequence called a replication signal--to sequester the virus's genetic material in compartments called spherules. "The spherules cloister the viral RNA, along with its copying machinery for replication, away from processes in the host cell that might otherwise degrade it," says Ahlquist. The team reports its results in the March issue of Molecular Cell.
This packaging-and-replication system, and the genes involved, is comparable to a quite different group: the retroviruses, of which HIV is the best known. Retroviruses use a similar set of components to seal off their RNA in structures called capsids. And a third group of viruses called double-stranded RNA viruses use a similar system. Together, these three groups make up half of all known viruses.
The shared packaging-and-replication mechanism could potentially be targeted by future drugs that fight a wide range of viruses. However, Ahlquist cautions that the finding's impact on basic science is more immediate. Robert Lamb, a virologist at Northwestern University in Evanston, Illinois, agrees. The study suggests that the three disparate classes of viruses stem from a common ancestor, says Lamb, and "presents an unexpected new paradigm for viral evolution that may date back to the beginning of the RNA world."
Institute for Molecular Virology