Imagine a killer virus lurking quietly in the shadows of your peripheral nervous system, waiting patiently for the signal to attack.
Once it receives the cryptic high sign, the ambush is on. The virus launches its assault on the motor neurons within the spinal cord and brain stem that control all voluntary and involuntary muscle behavior.
Then the nightmare, akin to the seemingly universal dream of running in quicksand with lead weights on your feet, really begins. A ghastly ascending paralysis sets in, starting with the feet and creeping upward. The fail-safe point is the diaphragm. If the virus and its paralyzing effects are not stopped before reaching the muscular membrane that keeps humans breathing, death is certain.
The virus is called herpes B and it’s one of several infectious diseases studied by renowned researchers from Georgia State University. Working in some of the most high-tech, high-security labs in the United States, they study viruses such as herpes B, rubella, West Nile, HIV/AIDS and even Cat Scratch Fever.
Their research focuses on the pathogenesis of disease at the molecular level, providing scientific building blocks in understanding how viruses work. Many collaborate with scientists from around the world in hopes of developing vaccines or drugs to better treat the diseases.
Herpes B is a naturally occurring virus in macaque monkeys, the most commonly used animal for biomedical research, but causes them little or no harm. When the virus crosses over into humans, however, 80 percent die from the infection. That creates critical implications for the field of health research.
“We don’t understand what alters the course of the infection in humans when we compare it to what we see in macaques,” says Dr. Julia Hilliard, director of Georgia State’s Viral Immunology Center and probably the world’s most renowned expert on the B virus. “It’s resulted in five deaths in the biomedical community in the past 15 years and we’d like to prevent that from happening again. If it happens again, we suspect that importation of macaques for biomedical research may be shut down altogether.”
The knowledge gained from studying such a potentially lethal virus has broad-ranging applications in designing systems to identify and control new pathogens encountered globally. Dr. Hilliard says most infections established in humans today were transmitted from a different species.
“When you have an agent that’s newly introduced in the population and just getting a foothold, some interesting things are about ready to take place,” she says. “So you learn about agents and how hosts adapt to agents, particularly from the outset. You discover how people adapt to the virus.”
Dr. Hilliard heads a lab team of 30 that includes scientists, graduate and undergraduate students, an M.D. and technical and administrative staff. They work in labs ranging from BioSafety Level 2 to 4. The BSL-4 lab provides the maximum level of safety and security for handling potentially lethal infectious agents such as herpes B. It is one of only a handful in the United States and one of only two currently operating at an American university.
Because herpes B became a regulated toxin under the Patriot Act of 2001, its handling, storage and transfer have fallen under strict regulations, according to Jeff Owens, Georgia State biosafety officer. “Since Sept. 11 and the anthrax attacks of 2001, there have been many challenges associated with the facility,” he says. “New processes had to be established with extensive training and oversight to provide the safest and most secure facility, while at the same time protecting personnel, the environment and the community.”
Dr. Hilliard’s research focuses on finding the “signature” of herpes B on a molecular basis — that is, the path it takes from the time it attacks the cell, moves into the cell and the results of that cellular invasion. “There is a dance that occurs between the agent and the cell that results ultimately in a net effect,” she says. “Either the cell wins at constraining the agent, or the virus wins by not being constrained, or they reach a happy symbiosis.”
By studying that sequence of events, Dr. Hilliard says researchers can develop strategies to control the virus, whether it is through use of a vaccine, a drug or simply switching the course of the virus within a host.
Herpes B can spread to humans only when monkeys shed the virus and pass it on through body fluids. Humans are most often infected through bites, scratches or splashes. However, the monkey’s shedding period is so sporadic and unpredictable that exposure to fluid doesn’t automatically mean it contains the virus. But because of the possible lethal consequences of infection, each exposure must be treated as a worst-case scenario.
First-aid procedures for potential contamination include washing the affected area with detergent or bleach for 15 minutes. A stout regimen of antiviral drugs may be prescribed if the patient presents symptoms, and the drugs have been used effectively to halt the ascending paralysis in some patients. There are 23 known survivors of B virus infection and activation, all tracked by Dr. Hilliard’s team.
Dr. Hilliard was working in a BSL-4 lab at the Southwest Foundation for Biomedical Research in San Antonio when she was recruited to Georgia State as a Georgia Research Alliance Eminent Scholar in 1998.
The initial investment to build the BSL-4 lab inside Georgia State’s Natural Science Center cost about $1 million, shared by the university and GRA. But Dr. Hilliard brought with her huge amounts of grant funding from the National Institutes of Health. She says it takes a minimum of $1 million a year of NIH grant money to run the facility, which includes two BSL-3 labs and a BSL-2 lab.
The Viral Immunology Center now acts as an NIH National Resource Center and the world’s front line diagnostic lab for herpes B, receiving anywhere from 20,000 to 30,000 samples each year from all over the world to test for the presence of the virus. About 1 percent test positive. Some samples come from travelers or military personnel who have been bitten by a macaque and are frightened they have been exposed to the virus.
“(B virus infection) is like the Exxon Valdez disaster,” Dr. Hilliard says. “It’s a low-frequency, high-consequence event.”
Story by John Allen
Photography by Meg Buscema