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Mutating viruses may help make antibodies




 

UPI Science News - LOS ANGELES, N.Y., March 14 (UPI) -- A rapidly mutating gene in a virus that preys on bacteria may help lead to a new way to create artificial antibodies, scientists in California reported Thursday.

This surprising mechanism may even be found in humans and other life, suggesting a new way of generating biological diversity, they said.

"The viruses are a treasure trove of fascinating biological mechanisms," said senior researcher Jeff Miller at the University of California in Los Angeles.

"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 evade 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.

"But not so fast... (the phage) is not so easily fooled," Hatfull explained.

"You can run but you can't hide."

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."

"The science is very well done in this paper," Hatfull told UPI. "This is a process that could have very easily been overlooked. Part of the future direction is to figure out how it works."

The researchers described their findings in Science.

(Reported by Charles Choi in New York.)



 


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Information in this article was accurate in March 14, 2002. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.