Mutating viruses helps produce antibodies

Scientists at the University of California reported that, a rapidly mutating gene in a virus that preys on bacteria may help lead to a new way to create artificial antibodies. This surprising mechanism may even be found in humans and other life, suggesting a new way of generating biological diversity.

Jeff Miller, author of this study, the viruses are a treasure trove of fascinating biological mechanisms. This was one of those efforts that we were continuously surprised by as we learned more.

The researchers studied the bacterial family known as Bordatella. The germs are responsible for very contagious and potentially lethal respiratory diseases such as whooping cough. Bordatella is afflicted by a plague of its own, a kind of virus known as a bacteriophage or "bacteria eater." This phage infects Bordatella using its tail-like structures, which latch onto a specific molecule on the bacteria's surface.

To avoid the virus, the bacteria frequently switches its surface molecules, much as a person might switch their locks to prevent someone with a key from getting in. "In the world of microbial biowarfare, standing still in the face of a ferocious viral attack is a recipe for disaster," explained microbiologist Graham Hatfull of the University of Pittsburgh.

Bordatella can switch between two distinct forms -- one for colonizing the respiratory tracts of its hosts, and one better adapted for life outside a victim. The surface protein the phage latches onto is only present when Bordatella is in its colonizing phase.

The investigators, along with collaborators at the University of California in Santa Barbara and in Cambridge, England, discovered one in a million phage could remarkably generate trillions of possible keys to latch onto Bordatella's surface. The virus therefore rapidly keeps up with any of the bacteria's attempts to evolve resistance, adapting to attack the microbe even when the germ is not in a host.

The scientists are coming up with biotechnology applications such as artificial antibodies from this mutation process by working with chemist Gregory Weiss of the University of California in Irvine. For instance, by taking the phage's tail-like protein and mutating it, they could come up with a chemical that could latch onto deadly toxins.

The researchers also suspect this highly targeted mutation process may exist in more than just viruses. "I would not be surprised if this turns up in genomes of other organisms," Miller said. They are beginning to examine the human genome for the genetic signatures of this mechanism, as well as yeast and fruit flies.

The details of how this mutation process works still are unclear, but unexpectedly it seems to involve an enzyme tied to deadly retroviruses, such as HIV, known as reverse transcriptase. The enzyme apparently analyzes a master copy of the gene for the tail-like structures to modify a second copy of the gene, which is the version the virus uses to create the trillion keys.