New Understanding Of Complex Virus Nano-Machine For Cell Puncturing And DNA Delivery

Funded primarily by the National Science Foundation and published in the January 31, 2002 issue of the journal Nature, the research describes for the first time how the virus uses a needle-like, biochemical puncturing device to invade its host.

"We show, in its entirety, a complex machine that allows a virus to efficiently infect its unfortunate host cell, the E. coli. The baseplate portion of the virus tail is essential in this process," says lead researcher Michael Rossmann of Purdue University. Rossmann conducted the research with colleagues Shuji Kanamaru, Petr Leiman, and Paul Chipman of Purdue University, Victor Kostyuchenko and Vadim Mesyanzhinov of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry (Russia), and Fumio Arisaka of the Tokyo Institute of Technology (Japan).

Because of increasing resistance of infectious bacteria to pharmaceutical antibiotics like penicillin, new antibiotic tools are needed. Bacteriophages may play a future role in controlling disease-causing bacteria. "Knowing the exact mechanism of T4 bacteriophage infectivity is a significant breakthrough. This information could eventually help in creating "designer viruses" that could be the next class of antibiotics," said Kamal Shukla, the NSF project officer for this research.

Although only about a hundred nanometers in length and width, bacteriophage T4 is considered the "Tyrannosaurus rex" of bacteriophages as it is one of the largest of the bacterial viruses. It is also a "tailed virus" because it has a tail with fibers that are used to grip its host. The tailed viruses are very common; up to one billion phages can exist in a milliliter of freshwater.

The T4 virus consists of a head, tail, baseplate, and tail fibers - six that are long, and six that are short. The long fibers first find the E. coli and make a loose attachment; then the short fibers fasten to get a tighter grip.

The baseplate is the "nerve center" of the virus. When the long and short fibers attach to E. coli, the baseplate transmits this message to the tail, which contracts like a muscle. The baseplate both controls the needlepoint of the tail and the cutting enzyme that make a tiny, nanometer-sized hole through the cell wall of the E. coli. The viral DNA is then squeezed through the tail into the host. The E. coli, thus infected, starts to make only new phage particles and ultimately dies. "Our research described for the first time the structure of phage baseplate proteins and their role in cutting through the host cell wall," said Rossmann.