The Catholic University of America

Oct. 25, 2007

CUA Biologists Help Discover A Viral Motor's Might

Professor Venigalla Rao

WASHINGTON, D.C.-A team of Catholic University biologists and physicists at the University of California, San Diego, has shown that a tiny viral motor generates twice as much power, relative to its size, as an automobile engine.

In their study, published Wednesday, Oct. 23, in the journal Proceedings of the National Academy of Sciences, the researchers, who include CUA Professor Venigalla Rao, UCSD Assistant Professor of Physics Douglas Smith, and UCSD graduate student Derek Fuller, measured the forces generated by a nanoscale motor that packs DNA into a virus during the assembly of an infectious virus particle.

They discovered that the motor is considerably stronger than any known molecular motors, including those responsible for muscle contraction. This power allows the virus to reel in its long genome with remarkable speed of "up to around 2,000 basespairs per second," said Rao.

"It is the equivalent of reeling in and packing 100 yards of fishing line into a coffee cup, but the virus is able to package its DNA in under five minutes," explained Smith.

To measure the forces, the team attached a strand of bacteriophage T4 - a tiny virus that infects E. Coli bacteria - to one microscopic bead and attached another bead to an empty viral capsid that contained the nanomotor at its mouth.

Using laser beams to hold onto each bead, they brought the DNA strand and capsid into proximity, then measured the resistance produced by the motor as it grabbed the strand of DNA and pumped it into the viral capsid, as well as the speed at which the DNA was pumped.

The T4 DNA-packaging motor was able to speed up and slow down as if it had gears. The researchers, who report that this is the first discovery of a molecular motor exhibiting widely variable speed, propose that the feature may permit DNA repair, transcription or recombination - the swapping of bits of DNA to enhance genetic diversity - to take place before the genetic material is packaged within the viral capsid.

"The dynamic variability of packaging rate makes sense because, in the infected cell, the DNA is not fed to the motor as a free molecule," explained Rao. "It is very likely a complex and highly metabolically active structure. Thus the motor needs to adjust the packaging rate to accommodate other processes."

This work lays the foundation for extending research to viruses that affect humans, such as adenoviruses, which cause colds, and herpes viruses, which cause chicken pox, shingles and cold sores.

"Historically, path-breaking work on bacteriophage assembly has led to breakthroughs in animal virus assembly," said Rao. "Since the assembly of herpes viruses very closely resembles that of bacteriophage T4, our work should provide important insights to set up herpes virus in vitro systems in the near future."

The work could ultimately lead to better ways of designing antiviral medications that target the DNA-packaging process to block the infection cycle by preventing viral assembly and interfering with the ability of the virus to inject its DNA into the cells it infects.

Other contributors to the study were Dorian Raymer of UCSD, and Vishal Kottadiel, doctoral student at CUA. The study was supported by the National Institutes of Health and the National Science Foundation.


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