Bentley Fane: How the Virus Concocts Its Amazing Survival Jacket

Fane arrived at The University of Arizona (UA) with a collection or viruses assembled at the University of Arkansas and the University of California, San Diego. Now a professor in the UA Department of Plant Sciences and a BIO5 member, he began new experiments on the complex, four-billion-year-old life story of the virus.

His work centers on how a virus assembles its hard jacket, called a capsid, which lets it survive when its genome slips out of our cells and into the hostile outdoors, riding on the particles in a sneeze or residing a door knob.

Fane says it is complicated work that yields no fast or easy answers.

“You sign on for life,” Fane said. “We are in it for the long haul. It’s a career in itself.”

For Fane, that career had its roots when he was a student at Brandeis University, studying Russian poetry, in particular the work of Anna Akhmatova, the pen name of a poet whose writings were banned by Stalin. If asked, he will, in impassioned Russian, quote her poem “The Last Toast” from memory, about Stalin and the Russian spirit, quickly translating: “I drink to our broken home, to the dolor of my life, and to our common loneliness . . .” But he also took enough science to enter MIT for his doctorate in biology, working on genetic analysis of protein folding. “Biochemistry was calling me,” he said.

Fane went on to post-doctoral work in 1989 at the University of California, San Diego, working with the noted Masaki Hayashi, studying virus assembly of the family known as Microviridae. Fane’s team, in collaboration with Dr. Ian Clarke, of the University of Southampton Medical School, helped isolate a new subfamily of the Microviridae called the Gokushoviruses, incorporating the Japanese for “very small.” They named one of them MH2K, using Hayashi’s initials and 2K for the year 2000.

This work is so recent, Fane said, because the Gokushoviruses were hidden away, infecting host bacteria that in turn replicate only inside other cells. “They are like the flea on the flea,” he said.

At his lab in BIO5’s Keating Building, Fane analyzes the assembly of a particular kind of virus−ones shaped like a soccer ball, with 20 flat surfaces, a shape called icosahedral−that assembles in an infected cell.

“In short, I investigate how the virus is put together in infected cells,” Fane says. “In a cell, they replicate, directing the synthesis of components of which they are made−proteins and their genomes.”

For its journey into the world, the virus that Fane studies must enclose its genome in a capsid, or jacket, made of 192 different interlocking protein molecules.

“They don’t just come together like magic,” Fane said. “It’s a directed process. When you build a building, you put up scaffolding, construct it, and then you remove it. Many viruses use a similar mechanism, scaffolding proteins that play the exact same role.”

With the Microviruses, Fane has been able to modify virus proteins, turning them into assembly inhibitors, antiviral proteins. One future application of his work may involve transgenic plants and plant viruses, something he is just starting to investigate. Fane hopes to come up with mutant proteins to interrupt the formation of the capsid. Inserting the gene making the mutant protein into a plant could prevent an infecting virus from replicating and starting new commando raids on other crops.

“It would poison the assembly process,” Fane said.

Bentley Fane’s faculty web site describes, on a molecular level, his work on assembly of proteins and nucleic acids into virions.
http://microvet.arizona.edu/Faculty/fane/fane.html

Fane exhibited small sculptures showing the shape and structure of viruses in a 2008 art show at The American Association for the Advancement of Science art gallery in Washington, D.C. http://www.aaas.org/news/releases/2008/0613art_exhibit.shtml

In a 2008 UA pod cast, Bentley Fane talks about his work with viruses.
http://uanews.org/node/20704

A UA press release on using a virus to make a plant self-destruct.
http://uanews.org/node/20506

Accomplishments
Bentley A. Fane, a professor of plant sciences, has been recognized as the top expert on Microviruses, the family of virus that he has studied with continuous funding from the National Science Foundation since 1993, with a focus on scaffolding proteins. He has organized international meetings of societies in the field of viral assembly.

He is a visiting scientist with rank of professor at the University Medical School, Southampton General Hospital, in the United Kingdom. He has won top teaching awards from the College of Agriculture and Life Sciences and the UA.

Fane was appointed by the National Science Foundation as the U.S. adviser for microbiology to the U.S.-Israeli Binational Science Foundation.

Fane holds a licensing agreement, together with his partners at the FDA and the NIEHS, for a mutational assay for use with øX174 transgenic mice.

Collaboration Snapshot
Bentley Fane collaborates with scientists throughout the world who study related fields, notably with Michael Rothman at Purdue, on atomic structure of viruses, and Ian Clark of the University of Southampton Medical School, on the Gokushoviruses.

At BIO5, he collaborates with Maggie So, combining his expertise in macromolecular biosynthesis with her expertise in infectious disease to study the genesis of pilii in gonorrhea and the assembly of the biomotors that drive them.