By Andy Evangelista

Charles Chiu, director of UCSF's Viral Diagnostics and Discovery Center

While the H1N1 virus certainly is tenacious, refusing to dwindle or go away, it has yet to prove more lethal than the regular seasonal flu.

But if the virus should do a Jekyll to Hyde, turning into a more monstrous bug, laboratory detectives like Charles Chiu will sound the alarm.

Chiu, an infectious disease expert who directs the University of California, San Francisco's Viral Diagnostics and Discovery Center, today studies strains of H1N1 to learn whether or not the virus is mutating into something more severe or deadly as it spreads into the population. That happened during the 1918 flu pandemic, when a flu virus possibly mutated and killed an estimated 20 million to 40 million people worldwide. Although there are no signs yet that H1N1 is changing, scientists are keeping a vigilant eye on the virus.

Chiu collaborates with international researchers to collect and compare strains — he now has about 40 — from H1N1 patients in Mexico, Canada and the United States. "We have the capacity to take tens to hundreds of samples and simultaneously determine their entire genome sequence," said Chiu. "By understanding the entire genome of these 2009 H1N1 strains, we can determine how rapidly the virus is changing over time, its propensity for developing resistance and its capacity to become more virulent."

Chiu is one of several UC researchers now probing, tracking and modeling H1N1 to unlock its mystery. By staying one step ahead of the virus, scientists can advise public health officials, who can then take appropriate measures to limit its spread. Another concern, said Chiu, is that changes in the virus could make it resistant to vaccines and the antiviral drug Tamiflu.

In addition to tracking H1N1, Chiu's research may also help explain the origins of the virus.

"We know that many of its genomic segments have come from swine, but this virus is a complicated virus, derived not only from swine, but also from birds and humans," he said. "Understanding where this virus originated can help us investigate or predict potential outbreaks in the future."

The ViroChip is a three-inch glass slide with 36,000 spots of DNA from all of the nearly 2,500 known viruses. It is used to analyze and characterize viruses.

The centerpiece in Chiu's lab is the ViroChip, a three-inch glass slide with 36,000 spots of DNA from all of the nearly 2,500 known viruses, whether human, animal, insect or plant. After putting a tiny specimen on the chip and feeding it into a microarray, scientists can analyze and characterize the virus. The ViroChip can also identify unknown viruses if they share a smattering of genetic code with a known virus.

UCSF professors Joe DiRisi and Donald Ganem developed the ViroChip. It was first used in 2003 to identify the virus causing severe acute respiratory syndrome, or SARS, in less than 24 hours after receiving a sample from the Centers for Disease Control and Prevention.

Since then, UCSF researchers have employed the technology to detect a new virus that appears to be linked to some cases of prostate cancer and another that causes respiratory and diarrheal disease in children. The center currently is studying rare and unusual strains of HIV from Cameroon, Africa.

UCSF researchers also used the ViroChip to uncover a virus that had been killing parrots and other exotic birds for more than 30 years. They developed a diagnostic test so that healthy birds, including some endangered species, can be protected from the sick ones.

The UCSF Viral Diagnostics and Discovery Center — partnering with Abbott, a global health company — opened this spring near its Mission Bay campus to help identify more unknown viruses, especially those that may be linked to acute and chronic diseases.

"We have seen a tremendous demand from around the world for help in identifying the cause of infectious diseases, in both humans and animals," said Chiu, who also is affiliated with the California Institute for Quantitative Biosciences, or QB3, a partnership involving UCSF, UC Berkeley and UC Santa Cruz.

"Charles Chiu's work beautifully illustrates QB3's commitment to preventive medicine, controlling health care costs and bringing the benefits of UC research to the general public," said Regis B. Kelly, director of QB3.

Around the time the center opened, Chiu received a call from a researcher in Mexico, and then one from Canada, about a new outbreak — a cluster of patients who had fever and other types of flu-like illness. "It turns out those were the initial cases of the 2009 H1N1 outbreak," he said.

Chiu already was working with Mexican researchers, looking for possible viral causes of a diarrheal disease in that country. "But upon learning about this outbreak, we decided to focus our efforts on this flu," said Chiu.

"We have a tool that can be deployed by public health agencies for surveillance. If you take a sample, it will tell you within 24 hours if it is H1N1 or some other novel strain of influenza," he said. "Or it can be used for surveillance of animal herds, such as swine herds, to look for the sources of these novel pandemic-causing influenza viruses."

The goal of the center, said Chiu, is to aid researchers and clinicians alike in pinning down viruses that are causing disease.

"Up to 25 percent of respiratory infections remain undiagnosed despite all of the testing that's done," Chiu said. "And it's even worse for liver and brain infections, where doctors are unable to diagnose the source more than 75 percent of the time.

"This technology offers the potential for a single test that can be done in a comprehensive, rapid and cost-effective manner."

Andy Evangelista is research communications coordinator in the UC Office of the President's Integrated Communications group.