A Good Year

By Eric Sauter

It's been a productive year for Anette Schneemann. Over the last 12 months, Schneemann and her colleagues have produced a total of 10 papers—seven published, two submitted, and one, on the anthrax virus, scheduled for submission next month. While all of these studies deal with some aspect of a class of viruses called icosahedral RNA viruses, a large portion concentrate on one in particular—the Flock House virus.

The Flock House virus, whose odd-sounding name could be reminiscent of a 1980s British pop group, is a nodavirus and a member of the Nodaviridae family, which also include lethal fish viruses that continue to disrupt fish farms from Asia to Europe. The Flock House virus, on the other hand, kills insects—the New Zealand grass grub to be precise.

"It's the very first thing everyone asks about my work," Schneemann says. "'The Flock House virus—is that the chicken coop virus?' Actually, the Flock House virus was named after a former agriculture research station on the north island of New Zealand. In the pastures surrounding the station, scientists found all these dead grass grubs and discovered this virus that had replicated and killed them."

Schneemann, who is an associate professor in molecular biology at The Scripps Research Institute and whose first name is pronounced "Anett-a," has been studying the Flock House virus for almost all of her adult life and has developed an abiding appreciation for its abilities.

"The Flock House virus is a clever virus, extremely simple yet exceptionally successful in its ability to propagate itself," she says. "Its genome is very small, with just three expressed proteins, yet it can reproduce itself 100,000-fold in an infected cell in 24 hours. I know of no other animal virus that does that."

"An Unresolved Mystery"

It is the virus's ability to reproduce, the sheer ingeniousness of its assembly pathway, that has held Schneemann in its sway. The Flock House virus carries only two genomic packets of RNA somehow packaged into a single virion (the complete virus particle as it lives outside the cell)—a process that Schneemann calls an "unresolved mystery in virology." Once solved, information from this case could apply to other RNA viruses that cause such lethal and disparate diseases as influenza, childhood diarrhea, and food poisoning.

While a number of viruses carry multiple RNA segments in their genome, it is still unclear exactly how these viruses know which proteins and segments they need to join together to replicate themselves in the host cell. What makes the Flock House virus attractive as a research target is the fact that it is safe for humans to handle (not so for grass grubs) and it carries only two RNA segments.

If scientists could understand how the virus selects those segments to package in that single virion, they could probably figure out how to interfere with the process. From there, a whole world of anti-viral therapeutic possibilities would open up. Schneemann's research has helped to pry open the door to this scenario a bit further, adding to the knowledge of how viruses function within the cell.

"What we've found initially in our research," she says, "is that there's nothing unusual in the virus RNA itself that plays a role in the selection process—the virus RNA is completely normal. What we did find is that the host cell contributes to the accuracy of the replication process by keeping the components localized—the coat-proteins and RNA segments are brought together within the cell. As these infection events unfold, the virus not only asserts temporal control, it also exerts spatial control by placing the coat-proteins and RNA next to one another, which helps the coat-proteins find the RNA.

"We think this is also true for other viruses, like polio viruses," she continues, "so these findings could help point toward the way to the development of vectors to generate new vaccines."

Falling Headlong for Science

Schneemann was born near Cologne and started out wanting to be a teacher when a childhood accident and a hospital stay steered her towards medicine. After a brief fling with math, she fell headlong for chemistry, which she pursued through university work in Cologne and in Freiburg. Then, armed with the American equivalent of a master's degree, she decided to come to the United States.

"I always liked to travel and wanted to see the world," she says, " so I thought of getting my doctoral degree somewhere else. I picked the University of Wisconsin at Madison because they had an exchange program with Freiburg."

Unknowingly, Schneemann had picked the state where, according to the U.S. Census Bureau, nearly 42.6 percent of the population was of German ancestry, making it the second most German-American state in the country  after North Dakota: "It was quite amazing. They had a union with a rathskeller [tavern] and a restaurant called the Essen Haus. I thought, 'What have I stumbled into?'"

In addition to an environment reminiscent of home, she had stumbled into an interest in disease-causing viruses and a collaboration with a group of crystallographers at Purdue University, where Jack Johnson (who would later help bring her to Scripps Research, where he is now a professor in the Department of Molecular Biology) was doing work that would eventually lead to his uncovering the structure of the Flock House virus. Schneemann arrived at The Scripps Research Institute in 1995, and used this structural information in her work.

"It goes back again to the fact that the Flock House virus is a very productive virus," she says. "We know the structure and we can produce the virus particles in a non-infectious form by using the coat-protein in absence of the genome."

These qualities are the heart of the avalanche of Schneemann's studies this year, which includes research on anthrax antitoxins.

Schneemann didn't really plan on publishing so much: "What happened was that many of these studies were in the works for a long time and they all happened to come together this year. I work with a great many scientists, so many of these papers are the result of these collaborations. Scripps Research is a place that fosters collaboration and I think it's a huge advantage in getting a lot done."

Send comments to: mikaono[at]scripps.edu

Associate Professor Anette Schneemann has been studying the Flock House virus for almost all of her adult life and has developed an abiding appreciation for its abilities. Photo by Kevin Fung.